PHYSICO-CHEMICAL CHARACTERISTICS OF THE OBTAINED

MICROSPHERES WITH DIFFERENT POLYMERS AND THE RELEASE OF

ACTIVE.

Dianelis Fernandez Mena, 1 Martha Gomez Lane, 2 Leopoldo Nez de la

Fuente, 3 Peaks Diana Ramos, 4 Antonio Moya and Aleida Chang Mirabal5
Valds6

Summary
The influence of various polymers of lactic acid and glycolic acid copolymer on the
physicochemical characteristics of the microspheres obtained by the method of
multiple emulsion and evaporation / extraction solvent. We compared the behavior
of each of these polymers, it was observed that the copolymers of lactic-glycolic
acid (RG-503 and RG-506) allow to obtain a more encapsulation percentage close
to 100% and the release profiles of the active principle from microspheres is much
better than in the other polymers studied.
Subject headings: microspheres; polymers; pharmaceutical technology; polyglactin
910/qumica; EMULSIONS / chemical, solvent / chemical; evaporation.
In modern drug delivery systems, the microspheres have remarkable
characteristics such as ability to modify certain parameters and biodistribution
kinetics of the transported molecules, allowing its application in the field of
selective and controlled administration of drugs, particularly in treatment of cancer,
diseases of the skin, mucosa and infectious diseases.
The microspheres are comprised of a wide range of polymers individually and / or
can be combined with natural and synthetic origin.
As for the materials of synthetic origin, a variety have been proposed for the
preparation of microspheres being widely used lactic acid and glycolic copolymer
being biodegradable, biocompatible and physically resistente.1
In this work we set out to evaluate the influence of the viscosity of polymers of poly
(L-lactic acid), DL-lactic acid, DL-lactic-co-glycolic physicochemical characteristics
of a product loaded microspheres and colored tracer soluble in water and analysis
of their release profiles.

Methods
Was used poly L-lactic acid (Resomer L-207), poly DL-lactic acid (Resomer R-202
and 203) and poly DL-lactic acid-co-glycolic acid (Resomer RG-503 and 506), the
Boehringer Ingelheim , polyvinyl alcohol (PVA), MW 15000, from BDH, sodium
chloride and dichloromethane (DMLC) from Riedel de Haen and glass vials of 10
mL capacity, colorless and hydrolytic I.
We used a polytron PT 100 for forming emulsions, Bioblock digital mixer for
evaporation of solvent, Janestki centrifuge for collection Haake rotoviscometer
M5/NV system for determining the viscosity of the oil phase, for the quantification
Product tracer spectrophotometer was used Spectronic Genesys 2 PC and a
thermostated shaker for the release profiles.

Preparation of microspheres
The microspheres were prepared by forming a multiple emulsion of water in oil in
water (w1/o/w2) and removing the solvent by evaporation / extraction according to
the technique reported in the literatura.2-6
For solutions of polymers with apparent viscosity of 250 mPa.s, shown previously
as the most suitable to achieve microspheres with physicochemical characteristics
required, the solutions were prepared with different concentrations of polymers and
the viscosity was determined using the rotoviscometer of Haake signature M5/NV
system.
With the apparent viscosity polymer solutions 250 approximately equal to the 5
mPa.s polymers studied, developed the method for obtaining the microspheres
using a volume ratio organic phase: aqueous phase and assessed 10:500
physicochemical characteristics of these. Assays were repeated until the ratio
organic phase: aqueous phase more suitable for each polymer.

Encapsulation efficiency

To calculate the efficiency of encapsulation was recorded in the absorption

spectrum of the visible area of the tracer product dissolved in water and TRIS
buffer pH 7.4 at a concentration of 20 ug / mL using a spectrophotometer
Spectronic Genesys 2 PC.

Calibration curve. We performed a calibration curve prepared from solutions of

concentrations between 4 and 20 ug / mL in methanol / DMLC (9:1), reading the
absorbance at the wavelength of maximum absorption (508 nm) given above.
Sample preparation. Was weighed 20 mg of microspheres loaded with the tracer
and dissolved product with a methanol / DMLC (9:1), and volume was completed to
100 ml with the same solution.

Release profile
Sample preparation. Was weighed 100 mg of microspheres and placed in
empolletas quantitatively transparent glass 10 ml capacity and was added one
volume of 5 mL of TRIS buffer pH 7.4. The hermetically sealed ampoules and
placed in a thermostated shaker at 37 C for 60 minutes horizontal movements.
At predetermined time intervals a vial was removed, filtered through the membrane
content of 0.2 micron cellulose nitrate and 2 ml aliquots were taken and volume
was 10 ml with TRIS buffer pH 7.4 to determining the content of tracer in the
solution product. For this calibration curve prepared with solutions of
concentrations between 4 and 20 ug / mL in TRIS buffer pH 7.4, by reading
absorbance at 508 nm.7-10
Results
Table 1 shows the polymers studied, the intrinsic viscosity values reported by its
supplier and the concentration of each solution to render apparent viscosity of
about 250 mPa.s.
TABLE 1. Intrinsic viscosity values of the different polymers apparent
Table 2 shows the results of the physicochemical study of the
microspheres made with polymer solutions in a ratio organic phase:
phase 10:500, except for the polymer R-202, in which it was necessary
5:500 is difficult because of solvent evaporation and the microspheres
obtained freely dispersed in the medium.

obtained
aqueous
to vary it
were not

TABLE 2. Physico-chemical study of the microspheres

Considering the encapsulation efficiency of the microspheres obtained with the
different polymers, we calculated the percentage of product released tracer time
intervals of 24 h during 10 days. The results of the release profiles shown in Fig.

Discussion
As can be seen in table 1, with increasing polymer intrinsic viscosity reported by
the supplier decreases in concentration of this solution to obtain the apparent
viscosity is required, hence it follows that it is essential to meet specifications
quality of the polymer employed.

In the tests to obtain the microspheres was necessary to make adjustments in the
art as in all assays except those conducted with the polymer R-202, the ratio
organic phase: aqueous phase was 10:500 and in this case it was necessary to the
organic phase to reduce 5:500 for the microspheres may be freely dispersed in the
aqueous medium after the complete evaporation of solvent. Also the amount of
product ranged tracer which remains constant for the ratio of this with respect to
the amount of polymer used to compare the efficiency of encapsulation.

Once all the variables defined in the process of obtaining assays were performed
in duplicate with each of the polymers and the results obtained are shown in Table
2. As shown in this table 2, the mean diameters of the microspheres and the
residual solvent do not differ between trials, being among the expected values, in
performance logic values are observed for the scale of work and better
encapsulation efficiency polymers met R-203, RG-503 and RG-506.

In the determination of the release profiles were obtained the results shown in the
figure, where we can observe that in the microspheres whose matrix corresponds
to the L-207 polymer product release no tracer during the studied time, not with
those of the other polymers. The best results were observed in the microspheres
composed of polymers of poly D, L lactic-co-glycolic acid.

However, as with the polymers R-202 and R-203 also showed a greater than 40%
release at 24 hours, it is considered necessary to study the in vitro behavior of the
polymer microspheres that release the 4 to determine some pharmacokinetic
parameters, which will help you decide which which of them are offering a product
with the desired therapeutic efficiency.

Summary

The Influence of various polymers of lactic acid and its copolymer With The
glycollic acid on the physical and chemical Characteristics of the Microspheres
Obtained by the multiple emulssion extraction method and the evaporation of the
solvent was EVALUATED. The behavior of each of These polymers was compared.
It was Observed That the polymers of lactic-acid glycollic (RG-503 and RG-506) to
allow a percentage of encapsulation Attain closer to 100% and That the release
profiles of the active principle from the microspheres is much better than in the rest
Studied of the polymers.
Subject
heading:
Microspheres;
POLYMERS;
TECHNOLOGY,
PHARMACEUTICAL; polyglactin 910/chemistry, EMULSIONS / chemistry;
SOLVENTS / chemistry; evaporation.

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