Formulation and evaluation of colon targeted tablets containing simvastatin solid dispersion

Abstract

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-activated implant surface promotes osteoblast differentiation in vitro

“…Both of these peaks were from C-O stretching of secondary alcohol according to Elbary et al. 30 Small peak shifts to lower wavelengths were observed on SVS-coated samples, yet, the occurrence of these shifts could be explained by the combination of two adjoining peaks in the SVS-coated samples. Nevertheless, in the high-frequency region above 3000 cm −1 , a peak corresponding to free alcohol O-H stretching at 3548 cm −1 on the pure SVS powder was shifted to 3448 cm −1 on the SVS-coated sample.…”

“…30,31 The spectrum of SVS-coated coins showed another peak at 1387 cm −1 , while two peaks at 1389 cm −1 and 1369 cm −1 were observed on pure SVS powder, both of which were due to C-H bending. 30,29 The peak at 1256 cm −1 on the coated samples was derived from a C-O-C lactone stretch and was resolved in two peaks at 2166 cm −1 and 1225 cm −1 on pure SVS powder. 30 The peak at 1162 cm −1 on pure SVS and 1159 cm −1 on SVS-coated samples was due to a C-O-C ester stretch.…”

“…The former represented an ester and the latter an aromatic carbonyl group. 28–30 The peak at 1461 cm −1 appeared on pure SVS powder at 1467 cm −1 and was derived from C-H methylene bending. 30,31 The spectrum of SVS-coated coins showed another peak at 1387 cm −1 , while two peaks at 1389 cm −1 and 1369 cm −1 were observed on pure SVS powder, both of which were due to C-H bending.…”

“…28–30 The peak at 1461 cm −1 appeared on pure SVS powder at 1467 cm −1 and was derived from C-H methylene bending. 30,31 The spectrum of SVS-coated coins showed another peak at 1387 cm −1 , while two peaks at 1389 cm −1 and 1369 cm −1 were observed on pure SVS powder, both of which were due to C-H bending. 30,29 The peak at 1256 cm −1 on the coated samples was derived from a C-O-C lactone stretch and was resolved in two peaks at 2166 cm −1 and 1225 cm −1 on pure SVS powder.…”

“…30,29 The peak at 1256 cm −1 on the coated samples was derived from a C-O-C lactone stretch and was resolved in two peaks at 2166 cm −1 and 1225 cm −1 on pure SVS powder. 30 The peak at 1162 cm −1 on pure SVS and 1159 cm −1 on SVS-coated samples was due to a C-O-C ester stretch. Also, a peak at 1053 cm −1 on SVS-coated samples appeared in two individual peaks at 1072 cm −1 and 1055 cm −1 for pure SVS powder.…”