Solid dispersions (SDs) of simvastatin with mannitol, Ineutic®, Pluronic® F-68, PEG 4000 and PVP K-30 were prepared and evaluated to deliver simvastatin to the colon in a pre-solubilized form. The formula of choice was compressed into fast disintegrating tablets using drug compatible excipients and was coated with Eudragit® S100 as a pH-responsive polymer. We investigated the effects of several variables related to both SD preparation (carrier type, combined carriers and drug to carrier ratio) and tablet coating (coat level and type of plasticizer) on drug dissolution. Differential scanning caloremitry (DSC) and scanning electron microscopy (SEM) proved drug amorphization in SDs. The 1:5 simvastatin/ Pluronic® SDs showed the greatest improvement in dissolution efficiency (12.2-fold) at the lowest carrier ratio. The coating level was critical for determining the duration of the lagphase. Best results were given by the 10% coat (20:2:1 w/w Eudragit S100/ triethylcitrate/ talc). This formula resisted pre-colonic pH values and showed an adequate lag time for the intended colonic targeting (4 h), followed by an immediate release phase (t50%=249 min) in pH 7.4. The proposed coated tablets may provide a colonic delivery system for simvastatin with improved bioavailability
Simvastatin is a well established oral antihypercholesterolemic agent. This study aimed to formulate simvastatin as orodispersible tablets. The drug was incorporated as a solid dispersion using Pluronic® F68 as carrier. Croscarmellose Na was used as superdisintegrant, microcrystalline cellulose as filler, PVP K-30 as binder and 1:1 magnesium stearate/talc mixture as lubricant. Box- Behnken design was adapted to explore the main and interaction effects of three independent formulation variables on the prepared tablets, namely superdisintegrant concentration (X1), lubricant mixture concentration (X2), and binder concentration (X3). A total of 13 tablet formulations were fabricated in addition, to two replicates of the center point to assess variability and experimental error. The selected dependant variables were the in vitro and in vivo disintegration times, dissolution rate at 4 min, and dissolution efficiency after 30 min. Wetting time, drug content, hardness and friability were also evaluated. Tablet formula, composing of 12% superdisintegrant, 2% lubricant mixture and 3% binder, showed the highest dissolution rate with an acceptable disintegration time (43 sec), hardness, and friability and was chosen as the best formula. An accelerated stability study was conducted for 6 months at 40°C/75% RH. Results showed no significant changes in any of the tested parameters
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