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Open accessJournal ArticleDOI: 10.5402/2012/813836

In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

20 Nov 2012-International Scholarly Research Notices (Hindawi Limited)-Vol. 2012, pp 813836-813836
Abstract: Alfuzosin, a selective alpha-1a antagonistis is the most recently approved AARAS, with limited cardiac toxicity and exclusively used for lower urinary tract syndromes (LUTS). In order to reduce pill burden and better patient compliance modified release (MR) formulations have been developed. Alfuzosin MR tablet was developed by the use of hot-melt granulation techniques using monoand diglycerides as rate controlling membranes to minimize health care cost and uses of costly excipients. The other purpose of the study was to evaluate in vitro-in vivo performance of the scale up batch in healthy human subjects for commercialization. The blend uniformity (mean ± RSD%), assay, cumulative percent dissolution at 24h, hardness, and friability of the biobatch were 100.2 ± 0.05%, 100.43 ± 0.023%, 93.98%, 4.5kg, 5min, and 0.08%, respectively. The in vivo pharmacokinetic parameters under fasting conditions between test and reference formulations (Uroxatral 10mg extended release tablets) were comparable. The 90% CI, geometric mean ratio (%) and power of Cmax, AUCT, and AUCI of the fasting study for the test and reference formulation were 99.03% to 122.78%, 109%, 0.998; 92.94% to 116.71%, 104%, 1; 98.17% to 124.01%, 110% 1, respectively. The scale up biobatch showed negligible difference in in vitro properties with respect to the pilot batch. The formulation developed with these agents was safe to use as there were no serious adverse events developed during the conduction of the clinical trial on the healthy subjects. Furthermore, the developed formulation was bioequivalent with respect to rate and extends of absorption to the reference formulation.

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References
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Book ChapterDOI: 10.1017/CBO9781139207249.009

[...]

01 Jan 2012-

123,310 Citations


Open accessJournal ArticleDOI: 10.1136/BJO.46.11.704

36,037 Citations


Open accessJournal ArticleDOI: 10.1023/A:1016212804288
Abstract: A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transport model and human permeability results for estimating in vivo drug absorption to illustrate the primary importance of solubility and permeability on drug absorption. The fundamental parameters which define oral drug absorption in humans resulting from this analysis are discussed and used as a basis for this classification scheme. These Biopharmaceutic Drug Classes are defined as: Case 1. High solubility-high permeability drugs, Case 2. Low solubility-high permeability drugs, Case 3. High solubility-low permeability drugs, and Case 4. Low solubility-low permeability drugs. Based on this classification scheme, suggestions are made for setting standards for in vitro drug dissolution testing methodology which will correlate with the in vivo process. This methodology must be based on the physiological and physical chemical properties controlling drug absorption. This analysis points out conditions under which no in vitro-in vivo correlation may be expected e.g. rapidly dissolving low permeability drugs. Furthermore, it is suggested for example that for very rapidly dissolving high solubility drugs, e.g. 85% dissolution in less than 15 minutes, a simple one point dissolution test, is all that may be needed to insure bioavailability. For slowly dissolving drugs a dissolution profile is required with multiple time points in systems which would include low pH, physiological pH, and surfactants and the in vitro conditions should mimic the in vivo processes. This classification scheme provides a basis for establishing in vitro-in vivo correlations and for estimating the absorption of drugs based on the fundamental dissolution and permeability properties of physiologic importance.

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Topics: Dissolution testing (66%), Biopharmaceutics Classification System (61%), Drug (51%) ...read more

4,662 Citations


Journal ArticleDOI: 10.1016/S0928-0987(01)00095-1
Paulo Costa1, José Manuel Sousa Lobo1Institutions (1)
Abstract: Over recent years, drug release/dissolution from solid pharmaceutical dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is developed or produced, it is necessary to ensure that drug dissolution occurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematical formulas that express the dissolution results as a function of some of the dosage forms characteristics are used. In some cases, these mathematic models are derived from the theoretical analysis of the occurring process. In most of the cases the theoretical concept does not exist and some empirical equations have proved to be more appropriate. Drug dissolution from solid dosage forms has been described by kinetic models in which the dissolved amount of drug (Q) is a function of the test time, t or Q=f(t). Some analytical definitions of the Q(t) function are commonly used, such as zero order, first order, Hixson-Crowell, Weibull, Higuchi, Baker-Lonsdale, Korsmeyer-Peppas and Hopfenberg models. Other release parameters, such as dissolution time (tx%), assay time (tx min), dissolution efficacy (ED), difference factor (f1), similarity factor (f2) and Rescigno index (xi1 and xi2) can be used to characterize drug dissolution/release profiles.

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Topics: Dissolution testing (69%), Dosage form (52%), Dissolution (52%)

4,326 Citations


Open access
08 Feb 2016-
Abstract: Remington's pharmaceutical sciences , Remington's pharmaceutical sciences , کتابخانه دیجیتالی دانشگاه علوم پزشکی و خدمات درمانی شهید بهشتی

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2,995 Citations