A pharmaceutical study on formulation of some antihypertensive drugs into orodispersible dosage forms / Tayseer Mohamed Abdelrazek Elnawawy ; Supervised Samia Abdelkader Nour , Dalia M. Ghorab , Abdelmonaem Swailam

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

This study aimed to improve the solubility and dissolution of olmesartan at pH 6.8 and to formulate the drug into ODTs. Enhanced solubility was noticed in presence of PEG 4000, PEG 6000, PEG 8000 or ÝCD (at concentrations 1%, 2%, 3%, 4% and 5%). The maximum solubility reached was 420 ug/ ml in 5% PEG 6000 solution. Solid dispersions were prepared both by solvent evaporation and fusion using PEG 4000, 6000 and 8000 at D/C ratio of 1:1, 1:3 and 1:5 for each. Inclusion complex formation by kneading using ÝCD at drug: carrier ratio of 1:1, 1:2, 1:3, 1:4 and 1:5 Solid dispersions prepared by fusion technique using PEG 6000 at D/C ratio of 1:3 and 1:5 showed maximum dissolution of 92% and 98%, respectively. The later one was subjected for physicochemical DSC, SEM, IR and PXRD studies revealing physical change without chemical changes. ODT were prepared by direct compression and lyophilization techniques. A 24 full factorial design was followed for ODT prepared by direct compression with independent variables (superdisintegrant %, potassium carbonate %, D/C ratio and camphor concentration) the responses studied were DP4 and disintegration time. ODT prepared using 8% crospovidone, 20% K₂CO₃, D/C=1:3 and 5% camphor were the best releasing 94% olmesartan after 4 minutes with disintegration time of 20 seconds. F11 (prepared using 20 mg gelatin, 8.86 mg glycine, 8.86 mg mannitol and 10 mg PEG 6000 per tablet by lyophilization.) was the best for this technique releasing 81.67% after 4 minutes and disintegrated after 27.17 seconds. Comparison via long term stability revealed the superiority of CP13. For further biological studies this formula was compared to Olmetec ® tablets by administration human volunteers in cross over design. It was found that tmax decreased from 2 hours to 45 minutes; however Cmax increased from 599.58 ng/ ml to 1037.767 ng/ml and having relative bioavailability of 148.854 %. Thus this introduced formula was capable of that is capable of fast disintegration with higher dissolution and enhanced bioavailability than the marketed generic product

Issued also as CD