تطوير وتقييم شكل صيدلاني جديد بخاصية التحرر الفوري (أقراص بريغابالين)
Formulation and Evaluation of Immediate Release Pregabalin Tablets
محمد سميح شفيق شناعة
MOHAMMED SAMIH SHAFIQ SHANAA
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Pregabalin is an anticonvulsant agent used for the peripheral and central neuropathic pain treatment, marketed as Capsule and Solution dosage forms. The purpose of this study is to develop an immediate release Pregabalin Tablet, as a new dosage form in the Palestinian market that is bioequivalent to the FDA approved Reference Pregabalin Capsules (Lyrica). Pregabalin drug substance and the finished product during the time of development were not described in either the British or US pharmacopoeia. The chemical and physical evaluation of bulk drug substance (Pregabalin) was accomplished following the manufacturer`s analytical method and specification. A new reversed-phase, isocratic LC method was developed and validated according to USP validation parameters, for the qualitative and quantitative determination of Pregabalin in pharmaceutical dosage forms using HPLC (LaChrome Elite) equipped with photodiode array UV detector. Mobile Phase is a mixture of Phosphate Buffer pH 6.9, and acetonitrile (94:6). Chromatographic System is Column: C-18 ODS 5 to 10µm in diameter (25cm X 4.6 mm id), detector: UV set at wavelength 210 nm, Flowrate: 1.5 ml / min and Injection Volume: 20 μL. Formula development was accomplished through a series of steps: Selection of excipients through compatibility studies, selection of manufacturing process and in-vitro comparison studies versus the reference product. Excipients compatibilities were studied by preparing a binary mixture of Pregabalin and excipient (1:1) then sealed in neutral glass vials and incubated at 40±2 °C/75 ±5% RH for 30 days. The mixtures were tested by means of FTIR for any possible interactions. The following excipients (Microcrystalline Cellulose, Pregelatinized Starch, Talc and Mg Stearate) were found to be compatible with Pregabalin.A series of pre formulation trials were composed and processed by direct compression method. Selection of formula was based on: Powder characteristics: (such as compressibility ratio, flowability, bulk density and tapped density), which would allow for a simplified method of manufacture, friability, hardness and disintegration of compressed tablets. The selected formulation was applied to prepare Pregabalin Tablets in two strengths, i.e. tablets containing 75mg/tablet and 300mg/tablet. They are prepared as dose weight proportional. The compressed tablets were film-coated with PVA based polymer by using water as solvent.The stability of film coated Pregabalin tablets were tested by incubating the finished products in their final package (PVC-Alum) at different storage conditions i.e. 25 ± 2 °C / 60 % ± 5% RH, 30 C ± 2 °C / 60% ± 5% RH and 40 C ± 2 °C / 75% ± 5% RH. Samples were tested biweekly for content of Pregabalin (assay), physical appearance, dissolution rate, and degradation products. Pregabalin Tablets proved to be stable in all aspects for the period tested (1 month) at all storage conditions. Biowavier study was performed between Pregabalin Tablets (75mg and 300mg) and the Reference Pregabalin Capsules (Lyrica 75 and 300mg Capsules) using paddle method rotated at 50 rpm in different dissolution media (0.06N Hydrochloric acid solution, Acetate buffer pH 4.5 and phosphate buffer pH 6.8. It was found that either Reference or Test products release more than 85% of their Pregabalin content in 15 minutes. As Pregabalin API, according to BCS is Class I drug and the dissolution profiles of Pregabalin Tablets is similar to that of Reference Pregabalin Capsules (Lyrica) under the same test conditions, and all excipients used are not suspect of having any relevant impact on bioavailability it is strongly believed that the developed Pregabalin Tablets are bioequivalent to the marketed Lyrica Capsules.