Drugs modified-release

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... 

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. 

Voltarol is a brand-name preparation for diclofenac (NSAID) and modified-release tablets are available in 75 mg and 100 mg strength. Nu-seals is a proprietary preparation of enteric-coated aspirin 75 mg. Fentanyl, co-codamol and Suboxone (buprenorphine and naloxone) consist of opioid drugs. 

Sprinkle administration-The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The applesauce should not be warm because it could affect the modified release properties of Ritalin LA. The mixture of drug and applesauce should be consumed immediately in its entirety. Drinking some fluids (eg, water) should follow the intake of the sprinkles with applesauce. The drug and applesauce mixture should not be stored for future use. 

Indiplon is rapidly absorbed (1-2 h) and eliminated (ti/2 =1.3 h). In-vitro studies on indiplon show two major metabolites A-demethylation due to CYP3A4/5 and Ai-deacetylation by carboxylesterases. Its short half-hfe has enabled the development of two dosing paradigms with different formulations (1) an immediate release formulation to improve sleep initiation and for dosing in the middle of the night, and (2) a modified release formulation, which provides for immediate release and sustained release of the drug to help with sleep initiation, duration, maintenance, and sleep quality (Neubauer,... 

Lee L, Kepple J, Wang Y, et al Bioavailability of modified-release methylphenidate influence of high-fat breakfast when administered intact and when capsule content sprinkled on applesauce. Biopharm Drug Dis-pos 24 233-243, 2003... 

It is critical, during initial process development, to give serious consideration to the amount of material that will be applied (especially for processes involving drug layering or those involved with the application of modified-release coatings to fine particle products, where required coating levels in excess of 50% are not uncommon). Key factors to be established are ... 

That said, the task should not be overcomplicated, and many good instances exist to illustrate successful conclusions to such efforts. For example, the data shown in Table 12 illustrate the scaling-up of the Wurster process in which an aqueous latex coating has been applied to drug-loaded pellets in order to prepare a modified-release product. It is appropriate to point out that since the 32" Wurster essentially comprises three 18" Wurster units, the airflow used in the former represents approximately a threefold increase over that of the latter, with the result that the spray rate is scaled... 

Table 13 Process Variables Used in the Development and Optimization of a Coating Process Designed for the Application of a Modified-Release Film Coating to Drug-Loaded Pellets...

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). 

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