Biopolymeric mucoadhesive bilayer patch of pravastatin sodium for Buccal delivery and treatment of patients with atherosclerosis

Abstract

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.

Keywords::

• Mucosal drug delivery
• buccal
• pharmacokinetics/pharmacodynamics
• bilayer
• sustained release

Acknowledgement

The authors would like to thank The Food and Drugs Laboratory, Vadodara, Gujarat (India) for conducting animal studies , Cipla Ltd. (Mumbai, India) for gift sample of Pravastatin sodium and Colorcon (Mumbai, India) for gift sample of HPMC K4M.

Declaration of interest

The authors reports no declaration of interest.