Release, drug formulation extended

Bailey DG, Arnold JM, Bend JR, Tran LT, Spence JD. Grapefruit juice-felodipine interaction reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol 1995 40(2) 135-140. 

Drug formulations Extended-release carbamazepine monotherapy has been assessed in the treatment of bipolar disorder in 27 children in an 8-week, open study [130 j. There was modest improvement in mania. Two participants withdrew because of rashes. There was a marginal increase in body weight and no changes in laboratory measures. 

Drug formulations Extended-release levetiracetam Once-daily extended-release levetiracetam as add-on therapy in relractory partial-onset seizures has been evaluated in a 12 week, double-blind, randomized, placebo-controlled trial in 158 patients [204. There were adverse events in 41 (53%) of those who used extended-release leve-tira-cetam and in 43 (54%) of those who used placebo the most common were somnolence, influenza, irritability, nasopharyngitis, dizziness, and nausea. 

Drug formulations Extended-release oxcarbazepine should cause fewer adverse effects because of the less marked peak serum oxcarbazepine concentration before metabolism to its active monohydroxy derivate. In an open study, 27 patients with difiicult-to-treat localization-related epilepsies who had been taking immediate-release oxcarbazepine were abruptly switched to extended-release oxcarbazepine in identical dosages and the concentrations of oxcarbazepine and its active metabolite were measured before and after the switch [229. The new formulation was associated with significantly fewer adverse effects and better quality of life, and this was explained by lower peak oxcarbazepine concentrations. 

As mentioned before, nifedipine was the first marketed dihydropyridine CCB. Initially, the drug indication was exclusively for angina, but the more recently developed extended release (ER) formulations are used off-label primarily for hypertension (Bayer, 2004). The extended-release tablets use a cellulose coat that extends their release time. The half-life of the ER formulation is reported as 7 h, whereas the immediate-release formulation has a half-life of 2 h (Bayer). 

This book is a companion volume to Pharmaceutical Technology Controlled Drug Release, Volume 1, edited by M.H.Rubinstein and published in 1987. It focused on the different types of polymeric materials used in controlled release. This book extends these concepts to include drug properties, design and optimization, coating, the effect of food and pharmacokinetics. It also reflects the growing interest in biodegradable polymers in oral and topical formulations and the use of sterile implants. 

Apparatus. The nature of the dosage form will determine the type of dissolution apparatus that will be used for method development and validation. The following questions must be asked when selecting the dissolution apparatus. Is it a capsule Will a sinker be required How stable is the drug substance after dissolution in the medium Is the formulation an immediate release or an extended release formulation Is this a transdermal patch ... 

H. R. Chueh, H. Zia, and C. T. Rhodes. Optimization of sotalol floating and bioadhesive extended release tablet formulations. Drug Dev. Ind. Pharm. 21 1725-1748, 1995. 

An NDA can be submitted for a previously unapproved new molecular entity, or for a new salt, new ester, prodrug, or other noncovalent derivative of a previously approved new molecular entity, formulated as a modihed-release drug product. The first modified-release drug product for a previously approved immediate-release drug product should be submitted as an NDA. Subsequent modified-release products that are pharmaceutically equivalent and bioequivalent to the listed drug product should be submitted as ANDAs. BA requirements for the NDA of an extended-release product are listed in 320.25(f). The purpose of an in vivo BA study for which a controlled-release claim is made is to determine if all of the following conditions are met. 

Bioavailability studies quantify rate and extent of absorption. They compare the efficiency of the disposition of several drug formulations, e.g. immediate-release vs. extended-release or capsule vs. tablet or tablet A vs. tablet B etc., or they compare the disposition of different routes of administration, e.g. oral vs. subcutaneous or oral vs. intravenous. According to the definition, a comparison to the intravenous bolus injection yields the absolute bioavailability. 

The study described here has a very complex design for its exploratory approach. It combines four different extended release formulations, each tested under fasting and non-fasting conditions, and compares the results to the immediate release drug product as the reference formulation. The bilayer tablets combines an immediate release component and an extended release component in one vehicle. In this project a close cooperation between the galenics department and the clinical pharmacokinetic function was mandatory. The in vitro/in vivo correlation was done by means of the deconvolution which is an appropriate surrogate to describe the in vivo dissolution. 

Deconvolution is used to evaluate in vivo drug release and drug absorption from orally administered drug formulations (i.e., extended release) when data... 

If absorption is slow, and the apparent absorption half-life is much longer than the elimination half-life, then the dose regimen can be based on the apparent half-life of the absorption phase. Changing the formulation is a relatively common approach that is taken for short-acting drugs to extend the duration of absorption. The elimination half-life of nitroglycerin is approximately 2 min. However, nitroglycerin from a transdermal formulation is slowly released, and therapeutic plasma concentrations can be maintained for 24 h. 

In oral products, hypromellose is primarily used as a tablet binder, in film-coating, and as a matrix for use in extended-release tablet formulations.Concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-granulation processes. High-viscosity grades may be used to retard the release of drugs from a matrix at levels of 10-80% w/w in tablets and capsules. 

Controlled dissolution from a formulation may be critical for the control of duration of drug action. Extended release formulations are useful for most drug delivery routes. 

Keywords Hydrophilic matrix Monohthic Drug delivery Extended release Formulation Cellulose ethers Hypromellose (hydroxypropyl methylcellulose,... 

Table 11.1 Advantages and limitations of a drug formulated into an extended release (ER) dosage form Clinical advantages...

Huang, Y, Knanvilkar, K., Moore, A.D. and HUliard-Lott, M. (2003) Effects of manufacturing variables on in vitro dissolution characteristics of extended release tablets formulated with hydroxypropylmethylceUulose. Drug Dev Ind Pharm, 29, 79-88. 

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