Lack of Dissolution protocols for selected dosage forms in USP 21 / NF 19

In the United State of Pharmacopoeia (USP); many of the drug formulations do not have any standard dissolution apparatus for the standardization. So many times manufactures get a chance to supply less drug quantity which is generally stated on the container.

Few of the dosage form are discussed here.

1. Dissolution of the topical dosage forms

Drug releases studies from gels, creams and ointments are found in same criteria. Study of the dosage form required during its development phase and as a routine quality control test for assuring uniformity of the finished products. Such studies provide helpful information about physiological parameters involved in the invivo pre-cutaneous absorption such as diffusion coefficient and the stability of drug in the specific vehicle required.

Although many investigators have conducted drug release rate studies from topical dosage forms, it appears that no single procedure yet described in USP.

According to FDA guidelines the most commonly used method as follows.

In vitro dissolution method for topical dosage method is based on open chamber diffusion cell system such as a Franz Cell system, fitted usually with a synthetic membrane. The test product is placed on upper side on the membrane in the open donor. Chamber of the diffusion cell and a sampling fluid is placed on the other side of the membrane in receptor cell. Diffusion of drug from topical product across the membrane is monitored by assay of sequentially collected samples of the receptor fluid.

Aliquots removed from the receptor phase can be analyzed for drug content by either UV-Visible spectrophotometry or by High Pressure Liquid Chromatography.

2. Dissolution of suppositories

It has been reported that fatty bases, such as cocoa butter tend to release hydrophobic drugs, which are highly soluble in the oily base, very slowly. Emulsification of the fatty base significantly improves the drug release rate. Incorporation of surface active agent was found to improve the release rate.

Many investigators have conducted deep research on the drug release from suppositories, but no single method has designed yet for the standardization.
One method determines the dissolution rate of suppositories; is based on dialysis technique which is not present in USP. In this method suppository placed in dialyzing bag made of special membrane or cellophane material. The bag is placed in a beaker or wide mouth bottle containing known amount of distilled water and the concentration of drug released is measured at successive time intervals.

Slight variation of the basket method of the USP-dissolution apparatus -1 is also frequently used. Hansan Research markets a basket apparatus for suppositories dissolution testing. Hansan‘s modified basket uses slot instead of mesh to provide suitable porosity. The use of such basket avoids the blocking of mesh opening of the regular USP basket when oil based suppositories are used. System has also the advantage of being capable of testing suppositories that float or have low specific gravity that interferes with the flow dynamic in the paddle method.

So, pharmacopoeial committee should include the apparatus for those dosage forms which can not be standardized from the rest of apparatus and also set the standard limits for the total drug release which will further prevent to produce false positive results.