Sei sulla pagina 1di 31

www.bpharmstuf.

com 1
Definition: It refers to the establishment of rational
relationship between a biological response produced
by a dosage form and a physico chemical
characteristics.
1. Quality control procedures
2. Tablet or Capsule disintegration
3. Instrumental methods of analysis

Dissolution Rate Test


•The rate of drug absorption
•Dissolution Profile Parameters
•In Vivo Performance
•Proper In-Vitro Dissolution Rate
- Correlate the data with the
bioavailability
•Buffer Solutions
Apparatus
Speed of Rotation
Temperature
pH
Samples
Dissolution Media
Sampling time
Percent coefficient

www.bpharmstuf.com 4
Important Purpose
1.Providing necessary process control
2.Determing stability of dosage form
3.Facilitatinmg certain regulatory determinations
Definition: In-vivo studies deals with the
evolution of bioavailability and bio
equivalence of pharmaceutical dosage forms
using parameters like AUC,Cmax etc..

PARAMETERS:
1.Drug concentration in plasma at each
sampling time
2.Apparent rate constant for elimination
3.Biological half life
4. Urinary excretion rate and amount
excreted in urine at infinity
Correlation:
Correlation is a measure of relationship between
two mathematical variables or measured data values,
which includes the Pearson correlation coefficient as
a special case

www.bpharmstuf.com 8
1.This is the highest category of relation which act as a
meaningful quality control procedure predictive of
invivo performance of formulation

2. The invitro curve at stimulated dissolution


conditions can serve as surrvogate for invivo
performance of formulations and no additional human
studies are needed to justify changes in manufacturing
site raw material are minor formulation changes.
1.It utilizes all data but is non unique as diferent
shaped absorption/dissolution curve could result in
same moment value.

2. This correlation alone fails to justify


formluations,modification ,manufacturing ,site change
,excipient source change etc…

3. It does not justify the extremes of qualtiy control


standards.
1. It does not reflect the complete shape of plasma
level curve which is the critical factor that defines
the performance of control release/sustained
release product

2. The correlation is non unique . Thus it can only serve


as a guide in formulation development and as a
qulaty control procedure.
Methodology for developing the
Correlation:

 Develop formulation with different release rate such


as slow,medium,fast or a single rate if dissolution is
independent.
 Invivo conc. Of plasma BA studies i.e.,
Wagnernelson method.
 The intensity factor = time for 50% absorption/ time
for 50% dissolution
Transform T to the corresponding invitro time point
applying the equation T= invivo time/intensity factor.

www.bpharmstuf.com 15
In-Vitro
Dissolution testing of product to asses release rates
under various conditions.
Plasma Level Data:
It is established both for a batch of
material.

1.Predictive Mathematical Model


2.Quality control tool.
3.Series of Dosage forms.

www.bpharmstuf.com 17
 Batch to Batch consistency.
Development of new dosage form.
Assisting validity.

Two Basic Approches:

Establishing a Relationship.
Data form previous bio-
availability.

www.bpharmstuf.com 18
Advantages

 It reflects complete plasma level curve.

Method of manufacturing raw material supplies.

Extremes of Q.C standards can be justified by


convolution or deconvolution procedure.

www.bpharmstuf.com 19
Drug or Product Requirements for an
IVIVC

• Caution, if narrow therapeutic range

• Linear pharmacokinetics

• Preferably BCS I or II

www.bpharmstuf.com 20
Data Requirements

In vitro data

• data from batches tested in vivo

• compendial method (justify other method)

• aqueous medium, n ≥ 12 (!), CV < 10%

• profiles of test products of the same type curve

• (difference factor f1, similarity

www.bpharmstuf.com 21
Data Requirements
In vivo data

• data from study in humans, n ≥ 6, fasted

• cross-over design

• formulations with different release rates

• reference formulation (solution, i.v. bolus)

• same moiety as measured in vitro

• (biobatch)
www.bpharmstuf.com 22
Mathematical Techniques
Assessment of in vivo drug release or absorption
from plasma profiles:

• Model-dependant
based on the mass balance among the pharmacokinetic
compartments
(e.g. Wagner-Nelson, Loo-Riegelman)

• Model-independant
based on Theory of Linear System Analysis
(Convolution / Deconvolution)

www.bpharmstuf.com 23
Purpose of IVIVC and BCS
 Reduction of regulatory burden: IVIVC in
lieu of additional in vivo experiments, leading
to
 Time/Cost savings during product development
Scale-up, post approval changes
Biowaiver

 Enhanced significance of in vitro testing


 Justification for “therapeutic” product quality

 therapeutically meaningful release specifications

www.bpharmstuf.com 24
Rapid and similar dissolution
High Solubility
High permeability
Wide therapeutic window
Excipients

www.bpharmstuf.com 25
Registration of Changes for Existing Products
where a Robust IVIVC can Substitute a
Bioequivalence Study

• Level 3 Changes (U.S.) [SUPAC]

• Type II Variations (European Union)

• (Line extensions (bracketing principle))

• Exceptions exist, e.g. narrow therapeutic range


drugs,
nonlinear pharmacokinetics

www.bpharmstuf.com 26
Specification Setting for Modified Release
Products (EMEA)

• Three points (20-30%, around 50%, more than 80%)

• No IVIVC: Justify that side-batches are bioequivalent


difference upper / lower limit: up to 20%

• Specifications must be met during shelf-life of


product

• IVIVC established: Predicted profiles from upper and


lower
release limits are in 20% range of AUC
www.bpharmstuf.com 27
CONCLUSION:

In recent times much efforts has gone into establishing the invitro invivo
correlations for different types of control release formulations.
Physico chemical propeties of the invitro environment are simulated with those
invivo followed by comparision of the invitro release profiles with the invivo
absoprtion profile.
The development of control release dosage forms has been a major step
forward for therapy. However, the challenge of overcoming the vagaries
of the gastro intestinal tract exists.

www.bpharmstuf.com 28
REFERENCES:

1.BIOPHARMACEUTICS AND PHARMACOKINETICS :


D.M.BRAHMANKAR
SUNIL B.JAISWAL

2.PRINCIPLE AND APPLICATIONS OF BIOPHARMACEUTICS


AND PHARMACOKINETICS
Dr.H.P.TIPNIS
Dr.AMRITA BAJAJ

3. In VIVO HYDRAULIC CONDUCTIVITY OF MUSCLE


El Rasheid Zakaria, Joanne Lofthouse, and Michael F.
Flessner

4. BIOPHARMACEUTICS AND PHARMACOKINETICS :


Venkateshwarlu

www.bpharmstuf.com 29
Any Queries???

www.bpharmstuf.com 30
THANK YOU

www.bpharmstuf.com 31

Potrebbero piacerti anche