Modified-release

There is some evidence that receptors for other neurotransmitters on 5-HT nerve terminals also modify release of 5-HT. These include nicotinic receptors (increase release from striatal synaptosomes), a2A-adrenoceptors (depress cortical release) and H3-receptors (cortical depression). Because changes in 5-HT release on activation of these receptors is evident in synaptosomal preparations, it is likely that these are true heteroceptors . 

Formulation Immediate- release I m med iate-rel ease and extended-release Extended-release Modified-release... 

MR Harris, I Ghebre-Sellassie. Aqueous polymeric coating for modified release oral dosage forms. In JW McGinity, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage forms, 2nd ed. New York Marcel Dekker, 1997, pp 81-100. 

R Sjoqvist, C Graffner, I Ekman, W Sinclair, JP Woods. In vivo validation of the release rate and pa-latability of remoxipride-modified release suspension. Pharm Res 10(7) 1020-1026, 1993. 

There are two specific guidelines on prolonged-release oral dosage forms (3AQ10a, adopted November 1992) and on modified-release products—oral dosage forms and transdermal dosage forms (CPMP/QWP/604/96, adopted July 1999). The advice in the two documents differs in a number of ways. 

The purpose of this section of an application is to establish that the proposed manufacturing process is suitable and that it will yield consistently product of the desired quality. The concept is closely related to GMP and the detail of conventional manufacturing process validation may not be required. However, data will normally be required for nonstandard manufacturing processes (particularly nonstandard sterilization processes) and for those aspects of manufacture that are critical in terms of product quality, e.g., in the manufacture of modified-release products the quality, safety, or efficacy of which will be affected by the method of manufacture. 

Modified-Release Drug Delivery Technology, edited by Michael J. Rathbone, Jonathan Hadgraft, and Michael S. Roberts... 

These enzymes (and transporters) exhibit differential expression at various sites throughout the GIT. For example, CYP3A4 expression is highest in the duodenum and lowest in the colon conversely, the expression of P-gp is greatest in the colon. This has implications for the gut wall first-pass extraction of drugs delivered by modified-release formulations, where the majority of the drug must be absorbed from the colon. 

The bacteria in the intestinal tract serve as another well-known source of luminal drug degradation [61], though this is only important for the colon region as the luminal concentration of bacteria is 104 to 109-fold higher in the colon compared with the small intestine. Thus, this aspect is only relevant for drugs that reach this region, for example, due to poor permeability, slow dissolution or delivery by modified-release formulations. Hydrolytic and other reductive reactions are predominantly mediated by bacterial enzymes, and a list of the most prominent types... 

Gotteries, J., Svenheden, A., Alpsten, M., Bake, B., Larsson, A. et al., Gastrointestinal transit of amoxicillin modified-release tablets and a placebo tablet including pharmacokinetic assessments of amoxicillin, Scand. J. Gastroenterol. 1996, 32, 49-53. 

Prostaglandins Various tissues Modifies release of histamine and serotonin from mast cells and basophils... 

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... 

Dissolution testing has become an important component of the assessment of the quality of solid oral dosage forms and oral suspensions. The basic procedures for these oral dosage forms have been extended to transdermal delivery systems as well. The release rate for modified-release oral dosage forms adds a level of sophistication to the concept of dissolution testing, setting acceptance criteria at multiple time points. 

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

There are a number of FDA regulatory guidances that are associated with IVIVC development and validation, as well as the application of IVIVC to SUPAC. The specific IVIVC guidance for oral modified-release formulations was first published in September 1997 (1). There are several guidances on SUPAC, including those for both modified release (2) and immediate-release solid oral dosage forms (3). The recent... 

Food and Drug Administration Guidance for Industry. SUPAC-MR Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation, October 1997. 

Committee for Proprietary Medicinal Products (CPMP). Note For Guidance on Quality of Modified Release Products A. Oral Dosage Forms and B. Transdermal Dosage Forms Section I (Quality), July 1999. 

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