Extended-release dosage forms

L. Krywczynski and D. P. Brozyna, Extended-release Dosage Forms, CRC Press, Inc., Boca Raton, Fla., 1987, pp. 1—19. 

Pharmacokinetic Model for Simulation of Concentration-Time Profiles for Orally Administered Extended-Release Dosage Forms... 

Additional criteria for waiver of evidence of in vivo BA/BE are given in 21 CFR 320.22 (d)(3). For certain solid oral dosage forms (other than a delayed or extended-release dosage forms), a waiver for the submission of in vivo evidence of BA/BE is possible if the drug product has been shown to meet the requirements of an in vitro dissolution test, which in turn has been shown to correlate with in vivo data. A biowaiver may also be addressed to a reformulated solid oral dosage form identical to another drug product except for color, flavor, or preservatives for which the same manufacturer has obtained approval, if BA data are available for the approved... 

For an extended-release dosage form, at least three test time points are chosen to characterize the in vitro drug-release profile for the routine batch-to-batch quality control for approved products. Additional sampling times may be required for formulation development studies, biopharmaceutical evaluations, and drug approval purposes. An early time... 

Biederman J, Quinn D, Weiss M, et al Efficacy and safety of Ritalin LA, a new, once daily, extended-release dosage form of methylphenidate, in children with attention deficit hyperactivity disorder. Paediatr Drugs 5 833-841, 2003... 

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

Skelly, J. P., et ah, Workshop Report Scaleup of Oral Extended-Release Dosage Forms, Pharmaceutical Research, 10(12) 1800-1805, 1993. 

Extended Release Dosage Form A dosage form that allows a reduction in dos-... 

For highly water-soluble compounds, dissolution and absorption usually are complete within a few hours or less (given that permeability is adequate). For compounds with short half-lives, repeated dosing may be required to maintain in vivo drug concentrations within therapeutical levels. In these cases, extended release dosage forms are suitable to overcome the frequent dosing problem, leading to better patient compliance. 

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. 

An f2 value between 50 and 100 suggests that the two dissolution profiles are similar, indicating the test formulation is bioequivalent to the reference formulation.1 There are a minimum of three timepoints in extended release dosage forms an early timepoint that detects dose dumping, a middle point, and a not-less-than (NLT) 80% point. More points may be added, especially for very long drug release testing periods. 

Gao, P., Nixon, P., and Skoug, J., Diffusion in HPMC gels. II. Prediction of drug release rates from hydrophilic matrix extended-release dosage forms, Pharmaceutical Research, Vol. 12, No. 7, 1995, pp. 965-971. 

Krdwczynski, L. Oral extended-release dosage forms principles of technology. In Extended Release Dosage Forms, Krowczynski, L., Ed. CRC Press, Inc. Boca Raton, FL, 1987 97-158. 

Skelly, J.P. Scale-up of oral extended-release dosage forms. Pharm. Res. 1993,10, 1800-1804. 

For extended-release dosage forms, in vitro-in vivo correlation may be used to establish acceptance criteria when human bioavailability data are available for formulations exhibiting different release rates. Where such data are not available, and drug release cannot be shown to be independent of in vitro test conditions, then acceptance criteria should be established on the basis of available batch data. Normally, the permitted variability in mean release rate at any given time point should not exceed a total... 

IVIVC studies are expected for NDAs for solid oral extended-release dosage forms. Regulatory agencies have an expectation that in vitro release (disso-... 

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