PHT 252 Dossary SURFACE TENSION ( )

Basmah Al-

Cohesive forces : are the forces that exist between molecules of one phase. Adhesive forces : are the forces that exist between molecules of two different phases. Surface tension: is the force per unit length (dyne/cm) that must be applied parallel to the surface so as to counterbalance the net inward pull of molecules of interface together. OR : Surface tension: is the force per unit length (dyne/cm) on the surface of a liquid which opposes expansion of the surface area. "# $# %# &# Methods of eter!ination of surface tension Drop weight method. Drop number method. Capillary rise method. Differential capillary height method.

"# ro' (ei)ht !ethod: The of a liquid is related to the weight of a drop of that liquid which falls freely from the end of a tube. Method: . !eigh an empty" clean and dry small bea#er. $. !eigh the bea#er with % drops of water added using the gi&en clean graduated ml pipette. ('ipette should be held &ertically while adding the drops of the liquid). (. )epeat steps * $ three times and calculate the a&erage weight of one drop (m ). w w$ m = % +. repeat steps ,( for the pro&ided sample (chloroform " d- .+. or ben/ene" d-%.0.1) using the same pipette and bea#er (washed with alcohol and dried) and calculate the surface tension of this sample using the equation2 m = (3q. ) $ m$ where2 is the surface tension of water (#nown reference). $ is the surface tension of the sample (un#nown). m is the mass (weight) of one drop of water. m$ is the mass (weight) of one drop of the sample. $# ro' nu!*er !ethod: The surface tension of un#nown solution ($) may be obtained by counting the number of drops (n) in a certain &olume of liquid (e.g." %.4 or ml) using a graduated pipette under similar conditions and a liquid of #nown surface tension ( ) must be similarly treated using the same pipette under the same conditions. The following equation will then be used2 nd = $ (3q. $) $ n d$ Method: . Count the number of drops (n ) of %.4 ml of water using a clean ml graduated pipette. (The pipette should be held &ertically).

$ PHT 252 Basmah AlDossary $. Clean and dry the same pipette with alcohol" and repeat step 5 for the pro&ided sample" chloroform (n$). (. 6se the pro&ided data in table and 3quation $ to calculate the surface tension of the sample. Ta*+e " ,i-uid !ater Chloroform 7en/ene .+. %.0.1 d n (d.ne/c!) .$.0

%# Ca'i++ar. rise !ethod: !hen a capillary tube of a radius (r) is placed in a liquid with density (d) and contained in a bea#er" the liquid generally rises up the tube a certain distance (h). 7y measuring this rise" it is possible to determine the surface tension of the liquid using the following equation2
=
$ hrdg

(3q. ()

!here2

is the surface tension of the liquid (dyne/cm). h is the height of the liquid in the capillary tube (cm). r is the radius of the capillary tube (Cm). d is the density of the liquid (g/Cm(). g is the acceleration due to gra&ity (10% Cm/sec$).

Method: . Clean the pro&ided capillary with the solution to be used. $. 8ttach the capillary to a ruler with a rubber band. (. 'lace the ruler with the capillary in 4% ml bea#er containing water (reference) perpendicular to its bottom. 7e sure that the capillary is 9ust abo&e the bottom of the bea#er. +. Determine the height (h ) after equilibrium. (The height is measured from the surface of the liquid to the mar# on the capillary). 4. Calculate the a&erage &alue of the radius" #nowing that the surface tension of water ( :$;) -.$.0 dyne/Cm at $4 oC" using 3quation 5 (2 =
$ hrdg

<. )epeat steps ,+ for the sample of chloroform or ben/ene using the same capillary tube (washed with alcohol and let dry) and calculate its using 3quation 5 (. &# ifferentia+ ca'i++ar. hei)ht !ethod: Two capillaries with different diameters are used in this experiment. The liquid will rise to height h in the narrower tube and to h$ (less than h ) in the wider tube. The difference between h and h$ is measured as accurately as possible. This experiment will be performed on solution with #nown surface tension ( ) and repeated for solution with un#nown surface tension ($). 6n#nown surface tension ($) can be calculated from the equation2 ( h h$ ) d = (3q. +) $ (h h$ ) $ d $ Method:

( PHT 252 Basmah AlDossary . 8ttach two capillaries of different radius to the ruler. $. )epeat steps ( * + as for the abo&e experiment. (. =easure the difference between h and h$ for the two capillaries dipped in water" then between h and h$ when dipped in chloroform or ben/ene. +. Calculate the surface tension of the sample from 3q. 5 + using the pro&ided data in table $. Ta*+e $ ,i-uid !ater Chloroform 7en/ene .+. %.0.1 h" h$ (d.ne/c!) .$.0

Re-uire!ents of the +a*#: . =a#e your calculations. $. Comment on the results including2 definitions of surface tension" cohesi&e and adhesi&e forces" and then ma#e a comparison between the (:$;) and (sample). N#0#1 (physical pharmacy" p.++<) (CCl+) - $<.. dyne/Cm (C:Cl() - $.. dyne/Cm (C<:<) - $0.1 dyne/Cm For the co!!ent: >f the of the sample is less than that of water" this may be due to that the cohesi&e forces between the sample molecules are less than the cohesi&e forces between water molecules. (>ncrease cohesi&e forces causes increase in surface tension and decrease in adhesi&e forces causes an increase in surface tension). !ater has the largest &alue of (.$.0 dyne/Cm) because the cohesi&e forces between water molecules are &ery strong due to the strong hydrogen bonds existing between water molecules. Resu+ts for the deter!ination of surface tension of ch+orofor!: "# 0. the dro' nu!*er !ethod: n (for water) - $? ? $ / ( - .< - $ drops n$ (for chloroform) - +<?+4?+< /( - +4 drops nd .$.0 +4 = = $ $ (C:Cl() - $0.4 dyne/cm. $ $ .+. $ n d$ $# 0. the differentia+ ca'i++ar. rise !ethod: ( h h$ ) d .$.0 ( .0 %.<) = = $ (h h$ ) $ d $ $ (%.< %.() $ .+. $ (C:Cl() - $<..4 dyne/cm. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

PHT 252 Dossary

+ INTERFACIA, TENSION ( A/0)

Basmah Al-

Interfacial tension: is the force per unit length existing at the interface between two immiscible liquid phases" and has the unit of dyne/Cm. >nterfacial tensions are less than surface tensions because the adhesi&e forces between two liquid phases forming an interface are greater than when a liquid and a gas phase exist together (increase adhesi&e forces cause a decrease in interfacial tension). >f two liquids are completely miscible" no interfacial tension exists between them.

eter!ination of interfacia+ tension *et(een t(o i!!isci*+e +i-uids Determine the interfacial tension between water and chloroform by #nowing the interfacial tension between water and ben/ene using the drop number method2 (C<:< / :$;) - (4 dyne/Cm (:$; / C:Cl() - A dyne/Cm d (C<:<) - %.0.1 g/cm ( " d (C:Cl() - .+. g/cm ( Theor.: This method is based on the drop &olume (&) of a liquid (density - d ) issuing from a small orifice (pipette) dipped in another liquid (density - d$). The interfacial tension between the two liquids can then be gi&en by2 (A/0) 2 3(d" 4d$) 5 The &alue of B can be determined for the two immiscible liquids and $ whose interfacial tension is #nown. This &alue can then be used to calculate the un#nown interfacial tension between a liquid and a third liquid (" pro&iding the experiment with liquids and ( are carried out under similar conditions to those for liquids and $ and using the same pipette (to remo&e the effect of radius). Materia+s and a''aratus: 7en/ene" chloroform" ml graduated pipette and 4% ml bea#er. 6rocedure: . Celect a clean ml graduated pipette and fill with distilled water (hea&ier liquid). $. Dip the pipette in ben/ene (lighter liquid) and count the number of drops in %.4 ml (or any fixed &olume). The pipette should be held &ertically. (. Calculate the &olume of each drop. (D - %.4 / no. of drops) +. #nowing that the &alue of (C<:< / :$;) - (4 dyne/Cm " calculate the B &alue from the equation2 (C787 / 8$O) 2 3(d" 4d$) 5 " where D is the &olume of one drop d is the density of hea&ier liquid d$ is the density of lighter liquid B is a constant 4. )epeat steps " $" and ( using the same pipette (washed with alcohol) filled with chloroform (hea&ier liquid) and dipped in a bea#er containing water (lighter liquid). Calculate the &olume of each drop. <. 6sing the &alue of B obtained from step 5 + and data listed in table " calculate the &alue of (:$; / C:Cl().

PHT 252 Dossary ,i-uids ben/ene / :$; :$; / Chloroform d (C<:<) - %.0.1 g/cm (" d (C:Cl() - .+. g/cm (" d (water) - g/cm(. d" 4d$

4 Ta*+e " 3 5

Basmah Al-

A/0 (4

Re-uire!ents of the +a*#: . =a#e your calculations. $. Comment on the results including2 definitions of interfacial tension" cohesi&e and adhesi&e forces" and then ma#e a comparison between the (:$; / C:Cl() and (C<:< / :$;) . N#0#1 (from physical pharmacy) (:$; / C:Cl() - ($.0 dyne/Cm For the co!!ent: >f the (:$; / C:Cl() is less than (C<:< / :$;)" this means that the adhesi&e forces between water and chloroform molecules are greater than those between ben/ene and water molecules. Resu+ts: Eo. of drops of water (%.4 ml) in ben/ene - 4 drops D of one drop of water - %.4 / 4 - %. ml (C<:< / :$;)- D(d Fd$) B (4 - %. ( ,%.0.)B B- $<1$.( Eo. of drops of chloroform (%.4 ml) in water - 1 drops D of one drop of chloroform - %.4 / 1 - %.%$< ml (:$; / C:Cl() - D(d Fd$) B - %.%$< ( .+., ) x$<1$.( - ($.0 dyne/Cm @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

< PHT 252 Basmah AlDossary ETERMINATION OF T8E CRITICA, MICE,,E CONCENTRATION (CMC) OF A SURFACE ACTI3E A9ENT 0: SURFACE TENSION MET8O A surface active agent: is a molecule or ion that has a certain affinity for both polar and non polar sol&entsG therefore" they arrange themsel&es at the interface and lower the surface tension. 8n alternati&e expression is surfactant or amphiphile. Curfactants when present in a liquid medium at low concentrations exist separately and are of such a si/e to be subcolloidal. 8s the concentration is increased" aggregation occurs o&er a narrow range of concentration. These aggregates are called micelles. The critical micelle concentration (CMC): is the concentration at which micelles are formed. ;r (it is the concentration of the surfactant abo&e which it will migrate to the bul# and start to form micelles and show the minimum &alue of surface tension). 8t low surfactant concentration" the surface tension of the solution decreases with the increase in concentration up to the formation of micelles. 8t C=C and higher concentrations" the surface tension shows no significant changes. 6rocedure: . Celect . clean test tubes. (!ash with distilled water). $. 'lace in each tube different concentration of sodium lauryl sulfate solution ranging from %.%%4H to %.4H" (using the pro&ided H stoc# solution of the surfactant. The total &olume in each tube is to be % ml. Consider the density nd = $ of the surfactant solution and water is equal (so the equation $ n d$ n becomes $ = ). n$ E.7." Ior calculation of the &olumes of the C88 and water" use the relation2 CD - C$D$ e.g." %.%%4H x % - x D$ D$ - %.%4 ml of surfactant (ta#en by a graduated pipette) then add 1.14 ml of dist water to complete to % ml total in the test tube. 8nd so on for the rest of concentrations. (. 8fter preparation of the tubes" mix and count the number of drops in %.4 ml of the mixture (ta#en by a clean pipette washed with the solution) for each concentration. Ctart from the lower conc to the higher. +. )ecord the results in a table form (see below) and calculate the &alue of surface tension obtained for each conc of C88. 4. 'lot the relation between the surface tension and conc of C88" and comment on the results.

PHT 252 Dossary Eo. $ ( + 4 < . Conc of C88 % %.%%4H %.% H %.%4H %.$H %.(H %.4H mls of C88 % %.%4 %. %.4 $ ( 4

. Eo. of drops in %.4 ml solution $ + . $% $% $%

Basmah Al-

mls of water % 1.14 1.1 1.4 0 . 4

$ =

n n$

.$.0 dyne /cm <<..( 4..$ +.. +% +% +%

For the co!!ent: Definition of C882 as mentioned abo&e. Definition of C=C2 as mentioned abo&e. 3xplanation of the cur&e2 the surface tension &alue decreases with increasing the conc of C88 (due to increase in adhesion forces) until a certain point (C=C) at which no further change in surface tension &alue is obser&ed with increasing the concentration of C88 (this effect is due to the formation of micelles). @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

0 PHT 252 Basmah AlDossary SO,U0I,I;ATION OF SA,IC:,IC ACI IN NON<IONIC SURFACTANT (T=EEN >?) Eon,ionic surfactants may act as wetting" emulsifying " and solubili/ing agents. ;ne of the properties of surfactants is their ability to increase the solubility of a sparingly soluble compound through micelle formation. 7elow the C=C" as the concentration of surfactant increases" the solubility of the compound shows slower increase. 8t the C=C range" a sharp increase in the solubility can be obser&ed due to micelle formation (which entraps the undissol&ed molecules and get them dissol&ed) and then le&el off. i.e." =icellar solubili/ation. 8mong the pharmaceutical applications of solubili/ation are the steroid hormones" oil,soluble &itamins and antimicrobial agents. Materia+s and a''aratus: Calicylic acid (solubility g in 44% ml water" i.e." slightly soluble ( 2 %% to 2 %%%))" tween 0%" E/ % Ea;: solution" phenolphthalein indicator" %% ml bea#er" $4% ml conical flas#s" % ml pipettes" 4% ml burettes" filter paper and funnels. 6rocedure: . Celect 0 clean conical flas#s" gi&e each flas# a number" and place exactly gm of salicylic acid in each flas#. $. 8s shown in the table" add different amounts of tween 0% and distilled water to each of the 0 flas#s so that2 The total &olume in each flas# is 4% ml. The conc of C88 ranges from ,0H &/&. (. Cha#e all of the flas#s for 4 minutes (sha#ing should be efficient). +. Iilter the mixture of each flas#. 4. Titrate % ml of each filtrate with E/ % Ea;: solution using phenolphthalein as indicator. (" !+ ?#" N NaO8 @ "%#> !) sa+ic.+ic acid). End point: colourless to faint pin#. <. )ecord the results in the table and calculate the amount of salicylic acid dissol&ed in 4% ml. .. 'lot the amount of salicylic acid dissol&ed &s. tween 0% concentrations" and comment on the results. 8mount of salicylic acid dissol&ed Conc of 3nd point mls of mls of E.P. F 4% Eo. C88 (mls of %. E C88 water mg/4% ml (H &/&) Ea;:) % % $ ( + 4 < . 0 $ ( + 4 < 0 .4 $ $.4 ( + ,,, %.4 4% +1.4 +1 +0.4 +0 +..4 +. +< .. $.$ $.4 ( (.+ (.0 4 4.$ %.4 +( <$.4 14 $$ $+. ($4 ((0

PHT 252 Dossary

Basmah Al-

For the co!!ent: Definition of C882 as mentioned before. Definition of C=C2 as mentioned before. Definition of micellar solubili/ation2 which is the solubility due to the formation of micelles. 3xplanation of the cur&e2 at low conc of C88" there is a slow increase in the solubility of salicylic acid" until a certain point (C=C) at which there is a sharp increase in the solubility of salicylic acid due to the formation of micelles. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

PHT 252 Dossary

Basmah Al-

6RE6ARATION AN STA0I,IT: OF CO,,OI S Dispersed systems consist of particulate matter #nown as the dispersed phase" distributed throughout a continuous phase" or dispersion medium. Dispersed systems are classified on the basis of mean particle diameter of the dispersed material: . =olecular dispersions (less than nm (mJ)). 3.g." ;$ molecules" ions. $. Colloidal dispersions (%.4 Jm to nm (mJ)). 3.g." colloidal sil&er sol" natural and synthetic polymers. (. Coarse dispersions (K %.4 Jm). 3.g." emulsions and suspensions. Types of colloidal systems: 1 !yophilic colloids: (solvent"loving) Colloidal particles interact to an appreciable extent with the dispersion medium. 8ttraction between the dispersed phase and the dispersion medium leads to sal&ation (formation of a sol&ent sheath around the dispersed phase). >t consists of organic molecules e.g." gelatin" acacia" albumin. Their stability depends on the presence of sol&ent sheath . if remo&ed" the sol will precipitate (unstable). # !yophobic colloids: (solvent"hating) There is little attraction between the dispersed phase and the dispersion medium. There is no sol&ent sheath around the particles. They composed of inorganic particles e.g." sil&er" gold" sulfur" and sil&er iodide. Their stability depends on the presence of the surface charges (the li#e charges produce repulsion which pre&ent coagulation of particles). The neutrali/ation of these charges (by an electrolyte) will cause instability of the sol (ppt or discoloration). $ Association colloids: These colloids consist of amphiphiles or surface acti&e agents. 6re'aration of +.o'ho*ic co++oids: "# Ferric h.droAide Fe(O8)% so+ ( B ve char)e): :eat 4% ml of distilled water on a hot plate for boiling. 8dd 4% ml of $H IeCl( dropwise (to a&oid formation of coarse aggregates) until a clear dar# red sol is obtained. $# si+ver tannate so+ (<ve char)e): To 4%% ml of distilled water" add $% ml %. E 8gE;( (pipette) and then add % ml of H tannic acid solution. :eat this solution to 0% oC . 8dd % ml of H Ea$C;( solution (pipette) dropwise with continuous stirring until a tea,colored sol is obtained. 6re'aration of +.o'hi+ic co++oids: "# )e+atin so+: Coa# 4 gm of gelatin powder in 4% ml water for 4 minutes.

PHT 252 Dossary

Basmah Al-

8dd .4 ml of water and heat the mixture on a hot plate with stirring until complete dissol&ing of gelatin. Cool" and ad9ust the &olume to $4% ml with water. Sta*i+it. of co++oids

"# Fe(O8)% so+ (usin) & M NaC+): Eo. Ie(;:)( sol Distilled water + = EaCl 4 ml 4 ml ,, $ ml 4 + ml ml ( ml 4 ( ml $ ml + ml 4 $ ml ( ml 4 ml 4 ml + ml < ml 4 ,, 4 ml

Eotice the test tube in which precipitation or discoloration may occur" whyA 'recipitation may occur due to the neutrali/ation of charge on Ie(;:)( sol. E.7." if an electrolyte with a higher &alency than EaCl is used (e.g." Ea$C;+)" less &olume will be required to induce the discoloration. $# Si+ver tannate so+ (usin) ?#" M NaC+): Eo. Cil&er tannate sol Distilled water %. = EaCl 4 ml 4 ml ,, $ ml 4 + ml ml ( ml 4 ( ml $ ml + ml 4 $ ml ( ml 4 ml 4 ml + ml < ml 4 ,, 4 ml

Eotice the test tube in which precipitation or discoloration may occur" whyA 'recipitation may occur due to the neutrali/ation of charge on sil&er sol. E.7." if an electrolyte with a higher &alency than EaCl is used (e.g." CaCl$ or 8lCl()" less &olume will be required to induce the discoloration. %# 9e+atin so+ (usin) ethano+): Eo. Lelatin sol 3thanol 4 ml 4 ml $ ml 4 % ml ( ml 4 4 ml + ml 4 $% ml

Eotice the test tube in which precipitation may occur" whyA 'recipitation may occur due to the remo&al of the sol&ent (water) sheath around gelatin sol. This sol can be redispersed again by the addition of water. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

PHT 252 Dossary

Basmah Al-

68ARMACEUTICA, SUS6ENSIONS A pharmaceutical suspension may be defined as a coarse dispersion of finely di&ided insoluble material randomly distributed in a liquid medium or a&ailable in dry form to be distributed in the liquid when desired. An ideal suspension should be: . 3asily redispersed by sha#ing" $. Chould remain suspended long enough to withdraw an accurate dosage" and (. Chould ha&e the desired flow properties (i.e." &iscosity)" so it is pourable" +. The particles in suspension should be small and uniform in si/e so that the product is free from a gritty texture. %locculated suspension system: >s the one in which the repulsi&e surface charges of the suspended particles ha&e been chemically neutrali/ed. ;nce these repulsi&e surface charges ha&e been neutrali/ed" the attracti&e MDan der !aalsM becomes dominant. 6nder these conditions" the particles may approach each other more closely and form loose aggregates" termed N flocsN. Deflocculated suspension system: 8re characteri/ed as dispersions in which the particles exist as single entities with high repulsi&e surface charges. >n contrast to flocculated systems" a deflocculated system exhibits well dispersed particles which settle singly but more slowly. The particles ha&e a tendency to form a sediment or ca#e that is difficult to redisperse. Characteristics of a CF+occu+ated s.ste!C: . 'articles form loose aggregates. $. )ate of sedimentation is rapid. 3ffect of gra&ity is dominant. (. Cuspension is somewhat unsightly due to the presence of an ob&ious supernatant layer abo&e a coarse sediment layer. This unsightly appearance can be minimi/ed by manipulating the formulation to achie&e the largest possible sediment &olume. >deally" the sediment &olume should encompass the entire &olume of the suspension. Characteristics of a C ef+occu+ated s.ste!C: . 'articles settle slowly. $. 'articles form dense" ca#e,li#e sediment which may be difficult to redisperse. (. Cuspension has pleasing appearance. Co!'oundin): The first steps in preparation are critical to ma#ing a good (no lumps) suspension. !eigh and place insoluble powders in mortar. Triturate to brea# up particles" include suspending agent if a powder at this step. Eow with trituration" add the wetting agent" i.e." glycerin or %,$% ml of the &ehicle if the wetting agent and/or suspending agent are already prepared" continue until smooth mucilage is formed. 8dd any flocculating or deflocculating agents next. Triturate

( PHT 252 Basmah AlDossary well. Lradually" add about (/+ of the &ehicle" pour suspension into graduate and wash mortar with portions of the &ehicle to OC to final &olume. Eva+uation of sus'endin) a)ents 8 demonstration will be set up to measure the effecti&eness of se&eral suspending agents against a control in distilled water. The agent with the target sediment height is a superior agent. Contro+: Calamine Distilled water q.s. to H Cuspending agent !ater (control) ,,, I $H 8cacia I +H I =ethyl cellulose 4H Tragacanth 7entonite $H I $H I (H I
se dim ent..height..(cm) Vu = total..height Vo

.$4g $4 ml Cediment height (cm)at each time (min) % 4 $% (% +4 <% 1% $+ h. w.

N#0#1 Cediment &olume ratio (I) -

Duestions: . !hat is the ma9or disad&antage of higher concentrations of suspending agentsA

$. Does addition of suspending agents ensure redispersibility after settlingA 3xplain. Redis'ersi*i+it. of sus'ensions

+ PHT 252 Basmah AlDossary >n groups" prepare the four formulations as shown below. 'lace in + clean bottles or cylinders and obser&e.

Ingredient Culfadia/ine 8lCl( solution B:$';+ solution Ea C=C . =' ($H) %.$H DCC solution q.s. to I (%.4 h) I ( h) I ( w) Ilocculation Ca#ing )edispersion 8ppearance 3xplanation

A .$ ,, ,, ,, <%

& .$ ,, ,, <%

C .$ ,, ,, <%

D .$ ,, %.4H <%

N#0#1 Culfadia/ine is a F &e charged particles (negati&e /eta potential). 8lCl( solution is a (cationic) ? &e charged flocculating agent. B:$';+ solution is a (anionic) F &e charged flocculating agent. DCC is a wetting agent (dioctyl sodium sulfosuccinateG aerosol ;.T.). Ea C=C is a suspending agent. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

PHT 252 Dossary

Basmah Al-

IS6ENSIN9 OF 68ARMACEUTICA, SUS6ENSIONS A# Ma)nesiu! Trisi+icate MiAture (061 "E>?) )x =agnesium trisilicate 4% g Pight magnesium carbonate 4% g Codium bicarbonate 4% g Concentrated peppermint emulsion $4 ml Double strength chloroform water 4%% ml !ater to produce %%% ml Cend2 4% ml. Cig. 4 ml to be ta#en when necessary. $.4 g $.4 g $.4 g .$4 ml $4 ml 4% ml

Ca+cu+ations and 'rocedure: . Calculate the amounts required for 4% ml of the mixture. The insoluble materials of magnesium trisilicate" light magnesium carbonate and sodium bicarbonate are diffusible powders (easily wetted with water)" so no need to add a thic#ening (suspending) agent to this formula. I - 4%/ %%% - %.%4 =ultiply the )x by Iactor. Dehicle (water) -4% F ($4? .$4) - $(..4 ml. $. >n a mortar" mix thoroughly the fine powders of magnesium trisilicate" light magnesium carbonate and sodium bicarbonate. (. 'our gradually with trituration about half of the amount of &ehicle to the powder mixture in step 5 $ in order to prepare at first a smooth paste and then a fine suspension de&oid of any lumps. +. dilute the formed paste with the amount of conc. 'eppermint emulsion and chloroform water until it becomes pourable. 4. Transfer to a cylinder. !ash the mortar with successi&e small amounts of water left" and mix the washings with the mixture prepared. 8d9ust to &olume. <. Transfer the mixture to a suitable bottle and write the label. Ro+e of each in)redient: . =agnesium trisilicate" Pight magnesium carbonate and Codium bicarbonate are diffusible materials that act as antacids. $. Concentrated peppermint emulsion is a fla&oring agent. (. Double strength chloroform water is a fla&oring agent" sweetening agent and a preser&ati&e. 9enera+ use: as antacid preparation. ,a*e+: white Cha#e 7efore 6se =agnesium Trisilicate =ixture ;ne tablespoonful to be ta#en when necessary. Eame2 Date2

PHT 252 Dossary

<

Basmah Al-

0# 6henacetin sus'ension iss )x 'henacetin i Llycerin =ethyl cellulose fl D>> 8romatic elixir to fl / >>> .=.ft. =ist. =ette. Dim. Cig. fl to be ta#en e&ery four hours for pain.

<g +g $0 ml 1% ml

(g $ g / .$4 ml + ml +4 ml

Ca+cu+ations and 'rocedure: . Calculate the metric equi&alents and prepare half the amount (I- /$). $. 'henacetin is a sparingly soluble powder so it is prepared as suspension using a dispersion stabili/er. (. =ethyl cellulose is used as dispersion stabili/er and is &ery often used in the form of mucilage in prescription compounding. Co the preparation can be handled by2 a) =ixing methyl cellulose thoroughly with /( of the required amount of water as hot water (0% to 1% oC). b) 8fter complete dispersion cool and immerse in a bea#er that contains crushed ice. c) 8dd the remainder of water as cold water drop by drop with continuous stirring till a clear gel is obtained. +. 'henacetin powder is weighed and triturated thoroughly in a mortar with glycerin into a fine paste. 4. 8dd methyl cellulose mucilage gradually with trituration. 8dd aromatic elixir and complete the &olume. <. Transfer to a clean bottle and write the label. ,a*e+ : white Cha#e 7efore 6se 'henacetin Cuspension ;ne teaspoonful to be ta#en e&ery four hours for pain. Eame2 Date2 9enera+ use: analgesic and antipyretic preparation. Ro+e of each in)redient: 'henacetin2 analgesic and antipyretic" acti&e ingredient. Llycerin2 sweetening agent" increase &iscosity"and le&igating (wetting) agent. =ethyl cellulose2 suspending agent. 8romatic elixir2 fla&oring and sweetening agent.

PHT 252 Dossary

Basmah Al-

C# Ca+a!ine +otion 06 "E>>: )x Calamine 4% g ..4 g Qinc oxide 4% g $.4 g 7entonite (% g .4 g Codium citrate 4g %.$4 g Piquefied phenol 4 ml %.$4 ml Llycerol 4% ml $.4 ml 'urified water to %%% ml 4% ml Cend2 4% ml. Cig. =D6 Ca+cu+ations and 'rocedure: . Calculate the amounts required for 4% ml of the lotion. I - 4%/ %%% - %.%4 =ultiply the )x by I. !ater - 4% F ($.4?%.$4) - +..$4 ml $. Triturate the calamine" /inc oxide and bentonite with a solution of sodium citrate in about (4 ml of purified water. (. 8dd the liquefied phenol" and glycerol. +. 8dd sufficient water to complete to the final &olume. ,a*e+ : red Cha#e 7efore 6se Calamine Potion To be used as directed. Date2

Eame2

9enera+ use: antipruritic " soothing and emollient preparation. Ro+e of each in)redient: Calamine2 soothing" and antipruritic agent. Qinc oxide2 astringent. 7entonite2 suspending agent. Piquefied phenol2 preser&ati&e. Llycerol2 emollient. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

PHT 252 Dossary

Basmah Al-

OINTMENTS Oint!ents: are semisolid preparations for external application to the body. Therapeutically" ointments function as protecti&es and emmolient for the s#in" but are used primarily as &ehicle or bases for the topical application of medicinal substances. Crea!s: are semi,solid emulsions containing suspension or solution of medicinal agents for external application. Creams (;/! type and !/; type) are employed as emollients. 6astes: are ointment,li#e preparations with thic#" &iscous and less greasy and more absorpiti&e than ointments" due to higher proportions of powdered ingredients such as starch" /inc oxide calcium carbonate" and talc in the base. OINTMENT 0ASES ;intment bases are classified into four groups according to their physical properties2 1 'leaginous ointment bases: These bases are fats" fixed oils" hydrocarbons or silicones. They are anhydrous" greasy" non,washable" does not absorb water" and occlusi&e (form a film on the s#in so it increases s#in hydrationby reducing the rate of loss of surface water). They should not be applied to infected s#in. They are water free" and aqueous preparations are incorporated into them in small amounts and with great difficulty. They are useful primarily for their emollient and occlusi&e effects. 3xamples2 'etrolatum EI and !hite ointment 6C'. # Absorption ointment bases: They are anhydrous but hydrophilic ointment bases" they can absorb se&eral times their weight of water to form water,in,oil emulsion. They are non washable" not water soluble" compatible with most medications and heat stable. Their composition &ariea" but usually contain a lanolin fraction and petrolatum. The addition of fatty alcohols to these bases" particularly stearyl and cetyl alcohols increases the water number of almost any absorption base. These bases are useful as emollients" and as such they can help incorporation into oleaginous bases. The aqueous solution is first incorporated into the absorption base to form !/; emulsion and the resulting semi,solid can then be incorporated into oleaginous base. 3xamples2 8nhydrous lanolin" :ydrophilic 'etrolatum 6C'" 8quaphor . $ (ater"soluble bases: These bases are anhydrous" water soluble" absorb water and water washable.

PHT 252 Dossary

Basmah Al-

They are either carbowaxes ('3L) or hydrated gums (7entonite" gelatin" cellulose deri&ati&es). They are frequently used in the incorporation of non aqueous or solid substances" as they soften too easily for the incorporation of aqueous liquids. 3xamples2 'olyethylene glycol ointment 6C'. ) *mulsion ointment bases: a (ater"in"oil emulsion bases: These are hydrous" hydrophilic" absorbs water" non water remo&able" with low thermal conducti&ity and occlusi&e. They ha&e the same properties as the absorption bases. They are used primarily as emollients. 3xamples2 Cold Cream. b 'il"in"(ater emulsion bases: These are hydrous" hydrophilic" absorbs water and water remo&able. They are more acceptable by patients because they are greasless" easily washable and with good texture. These bases may be used solely for their ability to absorb discharges from dermatological lesions. Eon ionic surfactants are often used with these emulsions because they are less irritated" less toxic and produce more stable emulsions than the ionic surfactants. Llycerin" propylene glycol or '3L must be added to slow the e&aporation of water from aqueous phase. 8lso" fatty alcohols are usually added to impro&e the texture and stabili/e the emulsion. 3xamples2 :ydrophilic ointment 6C'. 6re'aration of oint!ents ;intments are prepared by two general methods2 . =echanical incorporation and $. Iusion. The choice of the method depends upon the medication and the physical properties of the constituents of the base. 1 +reparation by Mechanical incorporation: =echanical incorporation is performed by trituration in a mortar" or on a glass slab with a spatula. >nsoluble powder is first triturated with small amount of le&igating agent. The le&igating agents could be an oil (mineral oil) when preparing oleaginous ointment or glycerin and propylene glycol when preparing hydrophilic ointments. !ater soluble salts can be dissol&ed in water and incorporated with anhydrous lanolin before being incorporated with oleaginous base. # +reparation by %usion: !hen wax" spermaceti or other hard" fusible bodies are to be incorporated with soft" oleaginous materials" they are melted on water bath to a&oid excessi&e temperatures" beginning with the material possessing the highest fusion point and

$% PHT 252 Basmah AlDossary adding the other ingredients in order of decreasing &alues" until the softer oleaginous and perhaps liquid ingredients ha&e all been thoroughly incorporated by stirring. The ointment should be stirred until it congeals to insure a homogenous preparation. 'owdered medicaments should be incorporated after the base congeals using a small portion of the base as le&igating agent. AN EFAM6,E OF O,EA9INOUS OINTMENT 0ASES (=hite Oint!ent US6) !hite bees wax 4% g !hite petrolatum 14% g Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . =elt white bees wax (higher melting point) in a suitable dish on water bath. $. 8dd white petrolatum (lower melting point)" warm until liquefied" then discontinue the heating. (. )emo&e from water bath" stir the mixture until it congeals. +. Transfer to a clean container (cup) and fix the label. ,a*e+: )ed !hite ;intment 6C' To be used as directed. Eame2 Date2 9enera+ use: 3mollient and a &ehicle for medicinal substances. AN EFAM6,E OF A0SOR6TION OINTMENT 0ASES (8.dro'hi+ic 6etro+atu! US6) Cholesterol (% g Ctearyl alcohol (% g !hite bees wax 0% g !hite petrolatum 0<% g Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . =elt white bees wax (higher melting point)" stearyl alcohol and petrolatum in a suitable dish on steam bath. $. 8dd cholesterol and stir until it completely dissol&es. (. )emo&e from water bath" stir the mixture until it congeals. +. Transfer to a clean container (cup) and fix the label. ,a*e+: )ed :ydrophilic 'etrolatum 6C' To be used as directed. Eame2 Date2 )x )x

PHT 252 Dossary 9enera+ use: 3mollient and protecti&e.

Basmah Al-

AN EFAM6,E OF =ATER SO,U0,E 0ASES (6o+.eth.+ene )+.co+ Oint!ent) 'olyethylene glycol +%%% +%% g 'olyethylene glycol +%% <%% g Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . =elt '3L +%%% (higher melting point) in a suitable dish on water bath. $. 8dd '3L +%%. (. )emo&e from water bath" stir the mixture until it congeals. +. Transfer to a clean container (cup) and fix the label. ,a*e+: )ed 'olyethylene glycol ;intment 6C' To be used as directed. Eame2 Date2 9enera+ use: 3mollient and a &ehicle for other medicinal substances. AN EFAM6,E OF =/O EMU,SION OINTMENT 0ASES (Co+d Crea! US6) Cpermaceti $4 g !hite bees wax $% g =ineral oil 4<% g Codium borate 4g 'urified water 1% g Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . )educe the spermaceti and the wax into small pieces. $. =elt them with the mineral oil in a suitable dish on steam bath. (. Dissol&e sodium borate in the purified water" warm to .% oC" (co&ered). +. Lradually add the warm solution to the melted mixture" stirring rapidly and continuously. 4. )emo&e from water bathG continue stirring until the mixture congeals. <. Transfer to a clean container (cup) and fix the label. ,a*e+: )ed Cold Cream To be used as directed. )x )x

PHT 252 Dossary Eame2 9enera+ use: 3mollient and cleansing cream.

$$ Date2

Basmah Al-

Notes: The emulsifying agent in this cream is the sodium soap formed by the reaction of sodium borate with the free fatty acids present in bees wax. Cpermaceti acts as a stiffening (solidifying) agent. Cold cream is called so due to the cooling sensation pro&ided by the slow e&aporation of water contained in the emulsion when the cream is rubbed on the s#in. Cold cream is usually applied at night. AN EFAM6,E OF O/= EMU,SION OINTMENT 0ASES (3anishin) Crea!1 8.dro'hi+ic Oint!ent US6) =ethyl paraben %.$4 g 'ropyl paraben %. 4 g Codium lauryl sulfate %g 'ropylene glycol $% g Ctearyl alcohol $4% g !hite petrolatum $4% g 'urified water (.% g Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . =elt stearyl alcohol and white petrolatum on steam bath. $. Lradually" add the other ingredients" pre&iously dissol&ed in water and warmed to .4 oC" (co&ered). (. )emo&e from water bathG continue stirring until the mixture congeals. +. Transfer to a clean container (cup) and fix the label. ,a*e+: )ed Danishing Cream To be used as directed. Eame2 Date2 9enera+ use: 3mollient cream. Notes: The emulsifying agent in this cream is sodium lauryl sulfate (non ionic surfactant). 'ropylene glycol is hygroscopic material that slows the e&aporation of water from the base and pre&ent rapid dryness of the cream. )x

PHT 252 Dossary

$(

Basmah Al-

Ctearyl alcohol impro&es the texture of the cream and act as a stabili/er for the emulsion. =ethyl and propyl barabens are preser&ati&es. Danishing cream is called so due to the disappearance of the cream after rubbing into the s#in (no shine effect). Danishing cream is usually applied during the day time.

Another 3anishin) crea! for!u+a RA Ctearic acid $%% g 'ot.hydroxide +g Llycerin +% g !ater .+< g 'erfume q.s. 'reser&ati&e q.s. Cend $4 g. (I - $4/ %%% - %.%$4" multiply by I) 6re'aration: . =elt stearic acid on water bath at .4,0% oC. $. =ix glycerin with water and then dissol&e B;: in the mixture" and heat to the same temperature. (. 8dd 5$ to 5 gradually with stirring on water bath for 4 min for complete emulsification. +. )emo&e from water bath and continue stirring until cooling. 4. Transfer to a clean container (cup) and fix the label. Co!'arison *et(een co+d and vanishin) crea!s properties *mulsion Type 'il content (ater content *mulgent Time of use Appearance -umectants Cooling effect Cold cream w/o 45-8 ! 25 ! $ees wa%& gl'cer'l monostearate *ight ,hin' -not easil' disappear. *ot incorporated Pro1ides cooling sensation ,anishing cream o/w "5-#5 ! 8 ! (l)ali soap +a' time /att' -disappear rapidl'. 0ncorporated *o cooling e22ect

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PHT 252 Dossary

$+

Basmah Al-

MET8O S FOR 6RE6ARIN9 EMU,SIONS "# Theoretica+ considerations: 8n emulsion is a dispersed system containing at least two immiscible liquid phases in which one liquid phase is dispersed in form of small globules throughout the other phase. The dispersed liquid is #nown as the internal phase" whereas" the dispersion medium is #nown as the external or continuous phase. Types of emulsions2 !hen oil is the dispersed phase and an aqueous solution is the external phase" the system is designed as an oil,in,water (;/!) emulsion. Con&ersely" when water or an aqueous solution is the dispersed phase and oil is the continuous phase" the system is designed as water,in,oil (!/;) emulsion. Due to the increase in the total surface area of the internal phase" the surface free energy will be increases. Therefore" emulsions are thermodynamically unstable and the dispersed droplets stri&e to coalesce (to come together) to reduce the surface free energy. >n order to minimi/e this effect" a third component" the emulsifying agent is added to the system to impro&e its stability. There are three classes of emulsifying agents2 ) Eatural emulsifying agents2 e.g." acacia" tragacanth" gelatin" eg yol#"R. $) Cynthetic emulsifying agents2 these include the anionic" cationic and nonionic surfactants" e.g." Tweens" Cpans" sodium lauryl sulfate. () Iinely di&ided solids2 e.g." 7entonite" magnesium hydroxide" aluminum hydroxide and magnesium trisilicate. The proper choice of emulsifying agent is frequently critical in de&eloping a successful emulsion. The choice of the emulsifying agent is critical to the preparation of an emulsion possessing optimum stability. Methods of e!u+sion 're'aration: a Dry gum method or Continental method: The emulsifier for the continental method is most often powder acacia" although other natural gums ha&e been used. The success of this method lies in the speed with which an emulsion may usually be formed. The s#ill required with this method is generally less than that required with the wet gum method" and ma#ing the primary or mother emulsion is the only crucial step in the technique. Ior both the wet and dry gum methods the ratio of oil/water/gum is +/$/ for fixed oils and $/$/ for &olatile oil. >n case of fixed oil" the powdered acacia ( part) is lightly triturated with four parts of fixed oil (or two parts of &olatile oil) in a dry mortar. !hen acacia is e&enly dispersed" two parts of water are added all at once with rapid trituration. The trituration is continued at high speed" using a spiral motion of the pestle" until a thic#

$4 PHT 252 Basmah AlDossary primary emulsion is formed. 8 snapping sound is heard when a good stable primary emulsion has been prepared. >t is during this process that the droplet si/e is reduced to its minimum dimensions and therefore" the time spent in this operation yields di&idends in stability of the final product. Iinally" the remainder of the aqueous phase is added slowly with trituration. b (et gum method or *nglish method: The technique of emulsion formation is suitable for preparing emulsions with mucilages or dissol&ed gums as the emulsifying agents and uses the +2$2 ratio as in the dry gum method. >t is necessary to use this method" although it is slower than and not as reliable as the dry method" if the emulsifying agent is a&ailable only in solution or if it must be dissol&ed before being used" as with perhaps methylcellulose. >n this method" a &iscous mucilage of the one part of gum is made with two parts of water and the oil is added in small amounts" with thorough" rapid trituration. !hen all of the oil has been added" the mixture is brought to &olume with water. c %orbesor bottle method of emulsification: 3mulsions which are to be made form &olatile oils (turpentine oil) or other &olatile components (chloroform) are most often made in a bottle. The main ad&antage is that the emulsion remains relati&ely fluid" and the &igorous sha#ing of a closed bottle impartssufficient shear,force to brea# down the oil droplet si/e. d -!& system (.riffin/s approach): >n the :P7 system" surface acti&e agents and oils are assigned a number (:P7 number). This number reflects the balance between the hydrophilic and lipophilic portions of the compoundNs molecule. The higher the number" the more hydrophilic the compound. The actual number has no significance" except as a means of ran#ing the surfactants. This ran#ing was based on extensi&e experimentations" as a result of which Lriffin was able to assign an application to the preparation of stable emulsion. The fundamental to the utility of the :P7 concept for preparing emulsion is the fact that the :P7 &alues are algebraically additi&e. Thus" by using surfactant with a low :P7 with one ha&ing a high :P7" it is possible to prepare blends ha&ing :P7 &alues intermediate between those of the two indi&idual emulsifiers that match the required :P7 &alue for the oil phase of a gi&en emulsion. Eaturally" the required :P7 &alue differs depending on wether the final emulsion is o/w or w/o. >f an o/w emulsion is required" the formulator should use emulsifiers with an :P7 in the range of 0, 0. ;n the other hand" if an w/o emulsion is desired" the formulator should use emulsifiers with an :P7 in the range of (,<. Ca+cu+ation of the a!ount of the e!u+sif.in) a)ents usin) 8,0 s.ste!: The preparation of an emulsion using the :P7 system in&ol&es the determination of the required :P7 of the oil phase" selection of twe emulsifiers (one of which has :P7 &alue lower than the desired :P7 while other has :P7 &alue higher than the desired :P7 ) and algebraically calculate a blend of the two emulsifiers that ha&e any :P7 &alue equal to that of the oil phase Mthe required :P7 &alueM. To illustrate this concept& the 2ollowing e%ample is gi1en: )x =ineral oil $4H ;li&e oil $4H 3mulsifier $H !ater q.s. <% ml

$< PHT 252 Dossary 'repare <% mls of o/w emulsion. i. ii. iii.

Basmah Al-

Bnowing that the :P7 &alues of mineral oil and oli&e oil are and 0 respecti&ely" then the required :P7 &alue should be 2 x %.4 ? 0 x %.4 - 1.4 Cince there is no commercially a&ailable emulsifier with :P7 &alue of 1.4" one can use a blend of Tween 0% (:P7 - 4) and Cpan 0% (:P7 -+.() to gi&e the desired :P7. 6sing the process of alternate allegation one can blend these $ emulsifiers in a mathematical proportion in such a way as to obtain a product whose :P7 is 1.4. Tween 0% (:P7) - 4 1.4 4.4 ,,,,, %.. H of Tween 0% to be used - (4.$/ %..) x %% -+0.<H H of Cpan 0% to be used - (4.4/ %..) x %% -4 .+H Therefore" the amount of Tween 0% - (<%x$/ %%) x %.+0< - %.40( g the amount of Cpan 0% - (<%x$/ %%) x %.4 + - %.< . g 6re'aration of e!u+sion usin) the 8,0 s.ste!: Lriffin suggested the following experimental procedure for the preparation of stable emulsions2 a. Lroup the ingredients on the basis of their solubilities in the aqueous and non aqueous phases. b. Determine the type of emulsion required and calculate an approximate :P7 &alue. c. 7lend a low :P7 emulsifier and a high :P7 emulsifier to the calculated &alue. Ior experimental formulations" use a higher concentration of emulsifier (e.g." %, (%H of the oil phase) than that required to produce a satisfactory product. 3mulsifiers should" in general" be chemically stable" non toxic" and suitably low in color" odor" and taste. The emulsifier is selected on the basis of these characteristics" on the type of equipment being used to blend the ingredients" and on the stability characteristics of the final product. 3mulsions should not coalesce at room temperature" when fro/en and thawed repeatedly" and at ele&ated temperatures of up to 4% oC. =echanical energy input &aries with the type of equipment used to prepare the emulsion. The more the energy input" the less the demand on the emulsifier. 7oth process and formulation &ariables can affect the stability of an emulsion. d. Dissol&e the oil,soluble ingredients and the emulsifiers in the oil. :eat" if necessary" to an approximately 4, % oC o&er the melting point of the highest melting ingredient or to a maximum temperature of .% to 0% oC. e. Dissol&e the water,soluble ingredients (except acids and salts) in a sufficient quantity of water. f. :eat the aqueous phase to a temperature which is ( to 4 oC higher than that of the oil phase. g. 8dd the aqueous phase to the oily phase with a suitable agitation. Cpan 0% (:P7) - +.( 4.$

$. PHT 252 Basmah AlDossary h. >f acids or salts are employed" dissol&e them in water and add the solution to the cold emulsion. i. 3xamine the emulsion and ma#e ad9ustments in the formulation if the product is unstable. >t may be necessary to add more emulsifier" to change to an emulsifier with a slightly higher or lower :P7 &alue" or to use an emulsifier with different chemical characteristics.

6RE6ARATION OF EMU,SIONS CONTAININ9 FIFE OI,S AN 3O,ATI,E OI, USIN9 =ET AN R: 9UM MET8O S "# a# E!u+sion containin) fiAed oi+ (,i-uid 'araffin E!u+sion): )x Piquid paraffin Caccharine sodium ( H solution) 8maranth solution Codium ben/oate 8cacia powder !ater to $% ml %.% 0 g %. ml %.< g q.s. <% ml

i. 'repare the emulsion using dry gum (continental method)2 ii. 'repare the emulsion using wet gum method (3nglish)2 Comment on the ease of preparation" &iscosity" and color of each sample. :and in the samples. Pabel them as2 dry or wet gum method. Ca+cu+ations: "# To prepare the primary emulsion (mother emulsion)" use the ratio2 oil 2 water 2 gum + 2 $ 2 (for fixed oils) $ 2 $ 2 (for &olatile oils) Cince the preparation contains a fixed oil (mineral oil or liquid paraffin)" then the ratio for the primary emulsion will be2 oil 2 water 2 gum + 2 $ 2 ;r $% 2 % 2 4 $# 8mount of saccharine sodium solution to be used - ( / %%) x %.% 0 - .0 ml. %# 8mount of &ehicle (water) to be used - <% F ($% ? .0 ? %. ) - (0. ml. The amount of water is to be di&ided into two portions2 % ml for the primary emulsion" and $0. ml for the dilution of the formed primary emulsion. 6rocedure: 1 preparation of the primary emulsion: a# 7y dry gum method2 >n a dry mortar" triturate the powder of acacia (4 g) with the $% ml of liquid paraffin until a smooth mixture is obtained.

PHT 252 Dossary

$0

Basmah Al-

8dd the % ml of water all at once with rapid and strong trituration in one direction until a thic#" creamy mass is produced and a snapping (clic#ing) sound can be heard. *# 7y wet gum method2 >n a clean mortar" triturate the amount of acacia (4 g) with the % ml of water until smooth fine mucilage is formed. =easure the amount of oil ($% ml) in a dry cylinder and add it gradually (drop wise) to the formed mucilage of acacia with trituration after each addition in one direction " until a thic#" creamy mass is produced and a snapping sound can be heard. # dilution of the formed primary emulsion: >n a small bea#er" dissol&e sodium ben/oate in the rest amount of water (S $0 ml)" then add saccharine solution and amaranth solution. Dilute the formed primary emulsion " gradually " by the abo&e solution with trituration after each addition. Transfer the final emulsion to a clean" dry bottle and fix the label. Cha#e 7efore 6se Piquid 'arrafin 3mulsion To be ta#en as directed. Eame2 Date2 9enera+ use: liquid paraffin emulsion is to be used internally as a laxati&e preparation in the treatment of constipation. >t is to be ta#en all at once. (Piquid paraffin acts as a lubricant). Ro+e of each in)redient: Piquid paraffin2 laxati&e" acti&e ingredient. Caccharine sodium2 sweetening agent. 8maranth solution2 coloring agent. Codium ben/oate2 preser&ati&e. 8cacia2 a natural emulsifying agent. "# *# E!u+sion containin) fiAed oi+ (Castor Oi+ E!u+sion): )x Castor oil < ml Lum acacia O.C. !ater to 0% ml %iat: 3mulsion. 0ig =DC 'repare the emulsion using the dry gum (continental) method. Ca+cu+ations: "# castor oil is a fixed oil " therefore" the primary emulsion formula to be used is2 oil 2 water 2 gum + 2 $ 2 (for fixed oils) <2 0 2+

,a*e+in): !hite

$1 PHT 252 Basmah AlDossary $# 8mount of &ehicle (water) to be used - 0% F (0) - .$ ml. The amount of water is to be di&ided into two portions2 0 ml for the primary emulsion" and .$ ml for the dilution of the formed primary emulsion. The dry gum method or wet gum method can either be used but the former is more suitable. 6rocedure: 1 preparation of the primary emulsion by dry gum method: >n a dry mortar" place + g of &ery finely pul&eri/ed acacia. =easure < ml of castor oil in a dry measure" and pour it on the gum in the mortar allowing time for the measure to drain. Triturate the oil and the gum together for few moments only (prolonged trituration at this stage is undesirable" since excessi&e of the oil and gum coats the gum particles so thoroughly with oil that the water cannot penetrate to them. Ior the same reason" failure may follow a long delay between mixing the oil and gum and adding water). =easure exactly 0 ml of water in another dry measure. 7egin to triturate the oil and the gum again using a whipping motion" not grinding action" and while triturating" add the water all at once. 8s water reaches the oil,gum mixture increase the rate of trituration " ta#ing care to wor# in one direction only and to maintain a whipping motion. Continue trituration until the primary emulsion is formed" which is indicated when the mixture becomes white in colour" and a clic#ing or crac#ing sound is heared. Continue the trituration for a little longer time before attempting to dilute. # Dilution of the formed primary emulsion: =easure % ml of water and add it dropwise" with continuous trituration" to the primary emulsion and then dilute with about % ml of water and transfer to a measure. )inse the mortar with more water and ad9ust to &olume. Transfer to a clean dry bottle and fix the label. ,a*e+in): !hite Cha#e 7efore 6se Castor ;il 3mulsion To be ta#en as directed. Eame2 Date2 9enera+ use: castor oil administered orally as a laxati&e. $# E!u+sion containin) vo+ati+e oi+ (Oi+ of Tur'entine E!u+sion): ;il of turpentine 8cacia powder !ater ad %iat: 3mulsion. 0ig =D6 )x 0 ml q.s. <% ml

(% PHT 252 Dossary 'repare the emulsion using wet gum method (3nglish).

Basmah Al-

Ca+cu+ations: "# Turpentine oil is a &olatile oil" therefore" the primary emulsion (mother emulsion) formula to be used is" oil 2 water 2 gum $ 2 $ 2 (for &olatile oils) 0 2 0 2+ $# 8mount of &ehicle (water) to be used - <% F (0) - 4$ ml. The amount of water is to be di&ided into two portions2 0 ml for the primary emulsion" and ++ ml for the dilution of the formed primary emulsion. 6rocedure: 1 preparation of the primary emulsion by 1et gum method: >n a clean mortar" triturate the amount of acacia (+ g) with the 0 ml of water until smooth fine mucilage is formed. =easure the amount of oil (0 ml) in a dry cylinder and add it gradually (drop wise) to the formed mucilage of acacia with trituration after each addition in one direction " until a thic#" creamy mass is produced and a snapping sound can be heard. # dilution of the formed primary emulsion: >n a cylinder" put the rest amount of water (S ++ ml). Dilute the formed primary emulsion" gradually" by the rest amount of water with trituration after each addition. 8d9ust to &olume. Transfer the final emulsion to a clean" dry bottle and fix the label. Cha#e 7efore 6se ;il of Turpentine 3mulsion To be used as directed. Eame2 Date2 9enera+ use: oil of turpentine emulsion is to be used topically as a counterirritant to increase the blood supply. 6RE6ARATION OF TUR6ENTINE ,INIMENT Piniments are alcoholic or oleaginous solutions or emulsions of &arious medicinal substances intended for external application to the s#in" generally by rubbing. Piniments may contain insoluble materials or they may consist of mixtures of immiscible liquids. !hen such conditions exist" it is best that an emulsion to be formed" if possible" to pre&ent rapid separation of the ingredients and to impro&e the appearance of the product. 3mulsification of liniments is usually accomplished by the formation of a soap which acts as the emulsifying agent.

,a*e+in): )ed

PHT 252 Dossary Tur'entine ,ini!ent 06 "E>>: )x Coft soap .4 g Camphor 4% g Turpentine oil <4% ml 'urified water $$4 ml %iat: liniment Mitte: 4% ml 0ig =D6 Ca+cu+ations: I - 4% / %%% - %.%4

Basmah Al-

(..4 g $.4 g ($.4 ml .$4 ml

6rocedure: This is an al#ali soap type of emulsion. . Iinely powder the camphor in a fairly large mortar" add the soap and mix well. $. 8dd the oil in small amounts" mixing well after each addition. !hen lumps ha&e been dispersed and a smooth suspension produced" the rest of the oil may be added quic#ly. (. Transfer the suspension to a bea#er for ease of pouring. 'lace all of the water in the formula into a bottle at least 4%H larger than the final &olume of the product. +. 8dd the oily suspension in small quantities" sha#ing &igorously after each addition. 4. Eote that if the oily suspension is placed in the bottle and the water is added" the emulsion will in&ert. <. >t is necessary to wait for the air generated by sha#ing to disperse before transferring the appropriate quantity to a calibrated bottle. ,a*e+in): )ed Cha#e 7efore 6se Turpentine Piniment To be used as directed. Eame2 Date2 9enera+ use: turpentine oil and camphor act as rubefacient and counterirritants.

PHT 252 Dossary

($

Basmah Al-

6RE6ARATION OF EMU,SIONS USIN9 8,0 S:STEM (0OTT,E MET8O ) Minera+ oi+ E!u+sion: =ineral oil 4%H 3mulsifier $H !ater q.s. ad <% ml 6sing a blend of Tween 0% (:P7 - 4) and Cpan $% (:P7 - 0.<)2 i. 'repare this emulsion assuming the required :P7 - 1" or ii. 'repare this emulsion assuming the required :P7 - " or iii. 'repare this emulsion assuming the required :P7 - (. Ca+cu+ations: "# 8mount of mineral oil to be used - (4%/ %%) x <% - (% ml. $# 8mount of emulsifier to be used - ($/ %%) x <% - .$ g. Tween 0% (:P7) - 4 %.+ 1 Cpan $% (:P7) - 0.< < ,,,,, <.+ )x

Therefore"

the amount of Tween 0% - ( .$ x %.+) / <.+ - %.%.4 g the amount of Cpan $% - ( .$ x <) / <.+ - . $4 g 8nd so on for the rest of the required :P7 &alues. %# The amount of water to be used - <% F((% ? .$) - $0.0 ml. 6rocedure: . =ix the amount of oil with the calculated amount of span $% in a small bea#er" then transfer the mixture to a clean" dry bottle. $. =ix the calculated amount of Tween 0% with that of water in a small bea#er. (. 8dd 5$ to 5 gradually (drop wise) with &igorous sha#ing after each addition. +. Iix the label.

PHT 252 Dossary ,a*e+in): !hite

((

Basmah Al-

Cha#e 7efore 6se =ineral ;il 3mulsion To be ta#en as directed. Eame2 Date2 9enera+ use: this emulsion is to be used internally as a laxati&e preparation in the treatment of constipation. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

ETERMINATION OF T8E REACTION RATE CONSTANT OF 8: RO,:SIS OF ET8:, ACETATE IN T8E 6RESENCE OF AN EDUA, DUANTIT: OF SO IUM 8: ROFI E C:(C;;C$:4 ? Ea;: ,,,,,,,,,,,,,, C:(C;;Ea ? C$:4;: The reaction depends on the concentration of both ethyl acetate and sodium hydroxide. >n this experiment" the concentration of both reactants are equal (a - b). The decomposition of ethyl acetate follows $nd order reaction #inetics2
% = 3t " where a (a %)

a x a,x B t

is the initial concentration of either reactant" is the concentration of the decomposed reactant" is the concentration of the remaining reactant" is the second order reaction rate constant" and is the time.

6rocedure: . >n two separate conical flas#s" place 4% ml of E/ % ethyl acetate and 4% ml of E/ % sodium hydroxide. $. 'ut % ml of E/ % :Cl and few drops of phenolphthalein in a titration flas#. (. Iill a burette with E/$% Ea;:. +. 8dd the solutions of 5 to one another" sha#e and quic#ly withdraw % ml to the titration flas# and titrate against E/$% Ea;:. 4. Co&er the reaction flas# and repeat the withdrawal and titration at the specified time inter&als ta#ing % ml at each time. Ca+cu+ations: :Cl is used to pre&ent further hydrolysis is E/ %" wheras Ea;: titrant is E/$%. Thus" the &olume of Ea;: will be double that of :Cl. Calculate the remaining sodium hydroxide after each specified time inter&al.

PHT 252 Dossary $% EP4ero moles / liter. $%% EPt EP4ero xmoles / liter. $%% a-

(+

Basmah Al-

'lot a cur&e for a ( a % ) against time and calculate the B &alue. The B &alue equals to the slope of the obtained line. The unit of B &alue is (mole. P , .min, ).

Ta*+e of resu+ts: Time (min) % 4 % 4 $% $4 (% 3' (ml) (.+ ..0 0.$ 0.0 1 1.( 1.( Clope 3' x f a x (moles/P) (moles/P) %.%(< %.%(< %.%(< %.%(< %.%(< %.%(< %.%(< % %.%$%1 %.%$(0 %.%$4< %.%$<< %.%$0% %.%$0%
% a(a %)

a(a,x) .$1 x %,( 4.+( x %,+ +..4 x %,+ (..$ x %,+ (.(0 x %,+ $.00 x %,+ $.00 x %,+

$..( <.1 ..$1 ..0< 0.%4 0.(+ 0.(+

% (0.++ +..1. <0..% .0.< 1..$$ 1..$$

Clope - B"

0$.4 4% = +.%< $% $

then B - +.%< mole. P, .min,

GGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGG

PHT 252 Dossary

(4

Basmah Al-

EFFECT OF TEM6ERATURE ON T8E RATE OF 8: RO,:SIS OF AS6IRIN 8spirin is stable in acidic medium and unstable in al#aline or aqueous medium. Cince aspirin is insoluble in water" sodium citrate can be used to dissol&e aspirin. The hydrolysis of ( molecules of aspirin in sodium citrate solution yield molecule of citric acid and ( molecules of acetic acid. 6rocedure: . >n a clean" dry stoppered measuring (&olumetric) flas#" place 4% ml of 4H sodium citrate solution ta#en by a burette. $. 'ut the flas# in a constant temperature water bath ad9usted at 4% oC. (. !eigh accurately g of aspirin. +. !hen sodium citrate solution reaches the assigned temperature (chec# by thermometer)" dissol&e the amount of aspirin weighed. Cha#e &igorously to dissol&e aspirin. 4. 8fter complete dissolution of aspirin" immediately" remo&e 4 ml sample (by pipette). )eturn the flas# to the water bath to #eep the temperature of the solution constant throughout the analysis time. <. 8dd the withdrawn sample to a conical flas# containing (% ml of distilled water and few drops of phenolphthalein indicator. =ix and titrate against E/ % Ea;:. The end point shows a change in the color of the solution from colourless to faint pin#. .. )epeat withdrawal of samples at the specified time inter&als and treat each sample as for the first sample. 0. Carry out the abo&e experiment at different temperatures" e.g." <% and .% oC. Thus three experiments are run together each one at either of the three temperatures. 1. )ecord the results of each experiment in a table form. Calculate the H remaining aspirin" plot the possible graph and estimate the reaction rate constant at each temperature (i.e." B 4% oC " B <% oC" and B .% oC ). %. >n order to ma#e the 8rrhenius plot for the reaction" calculate the corresponding log B at each temperature and the absolute temperature for the considered ( &alues then /T. . 'lot /T against log B. extrapolate the line obtained to room temperature. 3stimate the shelf life of aspirin solution at $4 oC.

PHT 252 Dossary

(<

Basmah Al-

Ca+cu+ations: 8spirin hydrolysis follows st order reaction rate #inetics2 Pog Ct - log Co F Bt / $.(%( Then slope - ,B / $.(%( 8nd B - slope x (,$.(%() 8spirin remaining at any time t (Ct) - $T,U H 8spirin remaining at any time t (CtH) $ 5 6 %% " where 5

T is the titer at time - % U is the titer at time - t. Tabulate the results" then plot log CtH against time and calculate the B &alue at the assigned temperature.

She+f +ife (tE?): is the time for the drug to reach %H decomposition or 1%H remaining. 8a+f +ife (t"/$): is the time for the drug to reach 4%H decomposition. For "st order reactions: t1% - %. %4 / B t /$ - %.<1( / B Arrhenius e-uation: Ea $.(%(7T 8rrhenius plot in&ol&es plotting log B against /T. The estimation of the shelf life of aspirin at $4 oC require the extrapolation of the line in the arrhenius plot to the absolute temperature corresponding to $4 oC. the &alue of log B at $4 oC is read and B &alue is estimated. Then the t1% is calculated from the equation2 t1% - %. %4 / B . log 3 = log ( Resu+ts "# The rate of h.dro+.sis of as'irin at H? oC: Time (min) % % $% (% +4 <% 3' (ml) +.0 +.1 4 4.( 4.4 4.. Ct +.0 +.. +.< +.( +. (.1 CtH %% 1..1 14.0 01.4 0 04.+ $ 0 .$ 4 Pog CtH $ .11 .10 .14 .1( .1

PHT 252 Dossary Clope .1< .1($ = .+04 % ( $4 +$.4

(.

Basmah Al-

B4% - $.(%( slope = (.+$ %( min

$# The rate of h.dro+.sis of as'irin at 7? oC: Time (min) % % $% (% +4 <% 3' (ml) 4 4.( 4.4 4.. < <.4 ClopeCt 4 +.. +.4 +.( + (.4 CtH %% 1+ 1% 0< 0% .% Pog CtH $ .1. .14 .1( .1% .0+

B<% - $.(%( slope = 4.<( %( min

.1 + .0.% = $.++ % ( (4 4(

%# The rate of h.dro+.sis of as'irin at I? oC: Time (min) % % $% (% +4 <% 3' (ml) 4. 4.4 <. <.4 . ..< ClopeCt 4. +.. +. (.. (.$ $.< CtH %% 1$. 4 0%.( 1 .$.4 + <$.. + 4%.1 0 Pog CtH $ .1< .1% .0< ..1 ..%

B.% - $.(%( slope = %.% Arrhenius '+ot:

.00$ ...% = +..<4 %( $4 +0.4

min

PHT 252 Dossary Temp. (oC) 4% <% .% T (oB) ($( ((( (+( /T (.%1 x %,( (.%% x %,( $.1 x %,(

(0

Basmah Al-

B (min, ) (.+$ x %,( 4.<( x %,( %.%

Pog B ,$.+. ,$.$4 , .1<

Ca+cu+ation of tE? of as'irin so+ution at $H oC: $4 oC - $10 oB. Then /T - (.(4 x %,( which is to be extrapolated to the line2 Then log B$4 - ,(.$ B$4 -<.( x %,+ min, . Therefore" t1% - %. %4 / B - %. %4 / <.( x %,+ - <<.+ min - $... h. @@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

EFFECT OF '8 ON T8E RATE OF 8: RO,:SIS OF AS6IRIN AT H?oC Method: . 8ccurately weigh %% mg (%. g) of aspirin. $. 'lace %% ml the buffer solution (p: (" <" 0" or %) in a constant temperature water bath ad9usted at 4% oC. (. !hen the buffer reaches the assigned temperature add to it the weighed aspirin. Cha#e to dissol&e. +. !hen complete dissolution is achie&ed" immediately remo&e ml sample (with a pipette)" transfer it to a dry cu&ette" add 4 ml colouring reagent and read the absorbance at 4+% nm (in a colorimeter) against a blan# consisting of the buffer solution ( ml) and 4 ml of the colouring reagent. 4. Camples are remo&ed at the following time inter&als %" 4" %" 4" (%" +4" <%" and 1% minutes from the beginning of the experiment. 3ach sample is to be analy/ed as for the first sample. <. Tabulate the results then plot log CtH &ersus time and calculate the B &alue at the tested p:. .. )epeat the abo&e experiment using buffer solution with different p:s. Calculate the B &alue at each p:" and then plot the p: F rate profile for aspirin. 3stimate the p: for maximum stability of aspirin.

(1 PHT 252 Basmah AlDossary Notes: 8spirin is more stable in acidic p: than in al#aline p:" since it is an acidic drug. (it is most stable at p: $.4 as shown in the p: F rate profile" ConnerNs). :ydrolysis of one molecule of aspirin (acetyl salicylic acid) yields one molecule of salicylic acid and one molecule of acetic acid. i.e." C1:0;+ m.wt aspirin 0% mg aspirin or .(%+ mg aspirin C.:<;( m.wt salicylic acid (0 mg salicylic acid mg salicylic acid

The colouring agent (IeE;() react with decomposition product (salicylic acid) to gi&e a color (&iolet) that can be measured colorimetrically. The intensity of the color increases with increasing the amount of salicylic acid in the sample. 8 uni&ersal buffer (Eo. () can be used for this experiment. The p: range of this buffer form $, $. Ca+cu+atios: 3ach absorbance is con&erted to concentration of salicylic acid by means of the slope of the standard calibration cur&e of salicylic acid. This slope equals to %.% 1. 6pon hydrolysis each molecule of aspirin yields one molecule of salicylic acid. Therefore" each one mg salicylic acid represents the hydrolysis of .(%+ mg of aspirin.

Resu+ts: "# 8.dro+.sis rate in *uffer so+ution '8 & at H? oC:

8sp. )emained (Ct) - %%, hydroly/ed 8sp. :ydroly/ed- conc of salicylic x .(%+

8bst,8bs%

a8st a8s% %.% 1

% % 4 (%

%.%%4 %.% %.% 4 %.%$

% %.%%4 %.% %.% 4

% %.$<( %.4$< %..01

% %.(+( %.<0< "%$1

%% 11.<4 11.( 10.1.

%% 11.<4 11.( 10.1.

.110 .11. .114

log CtH $

Conc of salicylic acid -

CtH- (Ct/ %%) x %%

8bs. at 4+% nm

Time (min)

PHT 252 Dossary +4 <% %.%( %.%(4 %.%$4 %.%( .( 4 .4.0

+% .. 4 $.%40 10.$0 1..1+

Basmah Al10.$0 1..1+ .11$ .11%

Clope - , ..( x %,+ B p: + - $.(%( x slope - (.11 x %,+ min, . $# 8.dro+.sis rate in *uffer so+ution '8 > at H? oC:
8sp. )emained (Ct) - %%, hydroly/ed 8sp. :ydroly/ed- conc of salicylic x .(%+

8bst,8bs%

a8st a8s% %.% 1

% % 4 (% +4 <%

%.% 4 %.%$ %.%( %.%44 %.%0 %.

% %.%%4 %.% 4 %.%+ %.%<4 %.%14

% %.$<( %..01 $. %4 (.+$ 4

% %.(+( .%$1 $..+4 +.+< <.4$

%% 11.<4 10.1. 1..$4 14.4( 1(.+0

%% 11.<4 10.1. 1..$4 14.4( 1(.+0

.110 .114 .10. .10% .1.%

Clope - ,+.(.4 x %,+ B p: 0 - $.(%( x slope - .%%. x %,( min, . Therefore" it can be noticed that aspirin is more stable in acidic p: (low B &alue) than in al#aline p:.

log CtH $

Conc of salicylic acid -

CtH- (Ct/ %%) x %%

8bs. at 4+% nm

Time (min)