Oral Sustained Release Tablet Containing Sildenafil Citrate for Pulmonary Arterial Hypertension: Formulation and in Vitro Characterization

Introduction: The aim of the present study was to develop the sustained release-(SR) matrix tablet of Sildenafil Citrate (SC), a cGMP-specific-Phosphodiesterase-inhibitor type-5 (PDE-Type-5) for relieving the symptoms of Pulmonary Arterial Hypertension-(PAH). The conventional tablets of SC, with dosing frequency thrice a day, has disadvantages like fluctuating drug plasma levels, unwanted side effects “Priapism” due to dose accumulation, cyanopsia. Here, an attempt was made to formulate the SR matrix tablet of SC, with hydrophilic polymers having 12 hrs release profile. Formulation components like polymers, binders and diluents were selected by comparing in-vitro dissolution profile with theoretical drug release profile-(TRP). Hydrophilic polymers like MethocelR K4M & MethocelR K15M, binders like polyvinyl pyrrolidone K30 & EthocelR Std 20 premium & Diluents like AvicelR PH 102, α– Lactose monohydrate & Dibasic calcium phosphate were investigated. All the batches were subjected for dissolution studies under simulated conditions. It was concluded that hydrophilic polymer (MethocelR K4M) was enough to sustain the drug release for 12hrs as solubility of drug decreases at basic pH. The best-assessed batch (D2) gave 98% drug release after 12hrs with MethocelR K4M having similarity factor of 86.88. The best-assessed batch followed zero-order release with anomalous transport indicating diffusion-relaxation controlled release. The optimized batch was reproducible showing similarity factor of 89 with good stability. In vitro dissolution studies showed that trial and error methodology has good potential to formulate and develop matrix tablet of SC without the need of complex design of experiments. 

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