DESIGN, DEVELOPMENT AND FUTURE APPLICATION OF MICROSPHERES

 

Drug release: [37]

In vitro methods
In vitro
drug release studies have been employed as a quality control procedure in pharmaceutical production, in product development etc. Sensitive and reproducible release data derived from physic-chemically and hydro dynamically defined conditions are necessary, however no standard in vitro method has yet been developed. Different workers have used apparatus of varying designs and under varying conditions, depending on the shape and application of the dosage form developed.

Beaker method
The dosage form in this method is made to adhere at the bottom of the beaker containing the medium and stirred uniformly using over head stirrer. Volume of the medium used in the literature for the studies varies from 50-500 ml and the stirrer speed form 60-300 rpm.

Interface diffusion system
This method is developed by Dearden & Tomlinson. It consists of four compartments. A represents the oral cavity, and initially contained an appropriate concentration of drug in a buffer. The compartment B representing the buccal membrane, contained 1-octanol, and compartment C representing body fluids, contained 0.2 M HCL. The compartment D representing protein binding also contained 1-octanol. Before use, the aqueous phase and 1-octanol were saturated with each other. Samples were withdrawn and returned to compartment A with a syringe.

Modified Keshary Chien Cell
A specialized apparatus was designed in the laboratory. It comprised of a Keshary Chien cell containing distilled water (50ml) at 370 C as dissolution medium. TMDDS (Trans Membrane Drug Delivery System) was placed in a glass tube fitted with a 10# sieve at the bottom which reciprocated in the medium at 30 strokes per min.

Dissolution apparatus
Standard USP or BP dissolution apparatus have been used to study in vitro release profiles using rotating elements, paddle and basket. Dissolution medium used for the study varied from 100- 500 ml and speed of rotation from 50-100 rpm.

In vivo methods
Methods for studying the permeability of intact mucosa comprise of techniques that exploit the biological response of the organism locally or systemically and those that involve direct local measurement of uptake or accumulation of penetrate at the surface. The most widely used methods include in vivo studies using animal models, buccal absorption tests, and perfusion chambers for studying drug permeability.

Animal models
Animal models are used mainly for the screening of the series of compounds, investigating the mechanisms and usefulness of permeation enhancers or evaluating a set of formulations.Animal models such as the dog, rats, rabbits, cat, hamster, pigs, and sheep have been reported. In general, the procedure involves anesthetizing the animal followed by administration of the dosage form. In case of rats, the oesophagus is ligated to prevent absorption pathways other than oral mucosa. At different time intervals, the blood is withdrawn analyzed.

Buccal absorption test
The buccal absorption test was developed by Beckett & Triggs in 1967. It is a simple and reliable method for measuring the extent of drug loss of the human oral cavity for single and multi component mixtures of drugs. The test has been successfully used to investigate the relative importance of drug structure, contact time, initial drug concentration and Ph of the solution while the drug is held in the oral cavity.

In vitro-In vivo correlations
Correlations between in vitro dissolution rates and the rate and extent of availability as determined by blood concentration and or urinary excretion of drug or metabolites are referred to as “in vitro-in vivo correlations”. Such correlations allow one to develop product specifications with bioavailability.

Percent of Drug Dissolved In Vitro Vs Peak Plasma Concentration
One of the ways of checking the in vitro and in vivo correlation is to measure the percent of the drug released from different dosage forms and also to estimate the peak plasma concentrations achieved by them and then to check the correlation between them.

Percent of Drug Dissolved Vs Percent of Drug Absorbed
If the dissolution rate is the limiting step in the absorption of the drug, and is absorbed completely after dissolution, a linear correlation may be obtained by comparing the percent of the drug absorbed to the percent of the drug dissolved. If the rate limiting step in the bioavailability of the drug is the rate of absorption of the drug, a change in the dissolution rate may not be reflected in a change in the rate and the extent of drug absorption from the dosage form.

Dissolution Rate Vs Absorption Rate
The absorption rate is usually more difficult to determine than the absorption time. Since the absorption rate and absorption time of a drug are inversely correlated, the absorption time may be used in correlating the dissolution data to the absorption data. In the analysis of in vitro and in vivo drug correlation, rapid drug absorption may be distinguished from the slower drug absorption by observation of the absorption time for the dosage form. The quicker the absorption of the drug the less is the absorption time required for the absorption of the certain amount of the drug. The time required for the absorption of the same amount of drug from the dosage form is correlated.

Percent of Drug Dissolved Vs Serum Drug Concentration
For drugs whose absorption from GIT is dissolution rate limited, a linear correlation may be established between the percent of drug dissolved at specified times and the serum drug concentrations at corresponding times.

Percent of Drug Dissolved Vs Percent of the Dose Excreted in urine
The percent of a drug dissolved and the percent of drug absorbed are linearly correlated. There exists a correlation between the amount of drug in body and the amount of drug excreted in the urine. Therefore, a linear relation may be established between the percent of the drug dissolved and the percent of the dose excreted in the urine.

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