Modified-release dosage forms

New decision rule and acceptance criteria Three case Policy proposed USP Guidelines revised 70 monographs now have standards Policy adopted January, includes the default First Case, monograph proposals published in June Policy proposed for modified-release dosage forms Revised policy adopted for modified-release forms Standards now in nearly 400 monographs field considered mature Chapter < 724 > covers extended-release and enteric-coated... 

USP. USP policy on modified-release dosage forms. Pharm Forum 1983 9(3) 2999-3001. 

In 1995, the FDA issued Scale-up and Post-Approval Changes (SUPAC) guidance for the industry (128) for immediate release dosage forms and in 1997, SUP AC MR guidance was released for modified release dosage forms (129). 

Establishing in vitro in vivo correlation (IVIVC) for modified release dosage form provides a justification for waiving in vivo bioequivalence evaluation only for certain specified post approval changes. Since a correlation is dependent on the mechanism of drug release, it is not used in situations that could potentially alter its mechanism (16). 

TABLE 2 Dissolution Conditions for Modified-Release Dosage Form... 

Note MR, Modified-release dosage form ER, extended-release dosage form DR, delayed-release dosage form IR, immediate-release dosage form. ... 

Modified Release Dosage Forms Dosage forms whose drug-release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms such as a solution or an immediate release dosage form. Modified release solid oral dosage forms include both delayed and extended release drug products. 

A report from a 1990 ASCPT/DIA/APS/FDA-sponsored workshop entitled 7n vitro/In vivo Testing and Correlation for Oral Controlled/Modified Release Dosage Forms (1990) concluded that, while the science and technology may not always permit meaningful IVIVC, the development of an IVIVC was an important objective on a product-by-product basis. Procedures for development, evaluation, and application of an IVIVC were described. Validation of dissolution specifications by a bioequivalence study involving two batches of product with dissolution profiles at the upper and lower dissolution specifications was suggested. 

Skelly, J. P., et al., September 1990, Report of Workshop on In Vitro and In Vivo Testing and Correlation for Oral Controlled/Modified-Release Dosage Forms, Journal of Pharmaceutical Sciences, 79(9) 849-854. 

This guidance recommends that dissolution data from three batches for both NDAs and ANDAs be used to set dissolution specifications for modified-release dosage forms, including extended-release dosage forms. 

Skelly, J.P. Report of workshop on in vitro and in vivo testing and correlation for oral controlled/modified-release dosage forms. Journal of Pharmaceutical Sciences 1990, 79 (9), 849-854. 

Drug Release from Modified-Release Dosage Forms... 

In suppositories cetyl alcohol is used to raise the melting point of the base, and in modified-release dosage forms it may be used to form a permeable barrier coating. In lotions, creams, and ointments cetyl alcohol is used because of its emollient, water-absorptive, and emulsifying properties. It enhances stability, improves texture, and increases consistency. The emollient properties are due to absorption and retention of cetyl alcohol in the epidermis, where it lubricates and softens the skin while imparting a characteristic velvety texture. 

In some instances, the product marketing authorization may be based on in vitro-in vivo correlation (IVIVC) information and in vitro data of modified release drug products, provided it is not the first (original) approval of the modified-release dosage form. 

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