Biopolymeric mucoadhesive bilayer patch of pravastatin sodium for buccal delivery and treatment of patients with atherosclerosis.
Mucoadhesive bilayer buccal patch has been developed to improve the bioavailability and therapeutic efficacy along with providing sustained release of pravastatin sodium. Buccal patches comprising of varying composition of Carbopol 934P and HPMC K4M were designed and characterized for surface pH, swelling index, in vitro bioadhesion, mechanical properties, in vitro drug release and in vivo pharmacokinetic and pharmacodynamics performance. All formulations exhibited satisfactory technological parameters and followed non-fickian drug release mechanism. Bilayer buccal patch containing Carbopol 934P and HPMC K4M in 4:6 ratio (PBP5) was considered optimum in terms of swelling, mucoadhesion, mechanical properties and in vitro release profile. Pharmacokinetic studies in rabbits showed significantly higher (p < 0.05) Cmax (75.63 ± 6.98 ng/mL), AUC(0-8) (311.10 ± 5.89 ng/mL/h) and AUC(0-∞) (909.42 ± 5.89 ng/mL/h) than pravastatin oral tablet (Cmax - 67.40 ± 9.23 ng/mL, AUC(0-8)-130.33 ± 10.25 ng/mL/h and AUC(0-∞)-417.17 ± 5.89 ng/mL/h)). While, increased tmax of buccal patch indicated its sustained release property in comparison to oral tablet. Pharmacodynamic studies in rabbits showed statistically significant difference (p < 0.005) in the reduction of TG (131.10 ± 10.23 mg/dL), VLDL (26.00 ± 2.56 mg/dL) and LDL level (8.99 ± 3.01 mg/dL) as compared to oral conventional tablet. In conclusion, bioavailability from the developed buccal patch of pravastatin was 2.38 times higher than the oral dosage form, indicating its therapeutic potential in the treatment of atherosclerosis.
TIFAC Center of Relevance and Excellence in NDDS, Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
Pramod
P
Yedurkar
Munish Kumar
MK
Dhiman
Kailash
K
Petkar
Krutika
K
Sawant
D000179:Acrylates / Q000737:chemistry*; D000278:Administration, Buccal; D000818:Animals; D019540:Area Under Curve; D050197:Atherosclerosis / Q000188:drug therapy*; D001682:Biological Availability; D016503:Drug Delivery Systems; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D009061:Mouth Mucosa; D017035:Pravastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D012995:Solubility
D000179:Acrylates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C453622:carbopol 934P; D017035:Pravastatin