Development and evaluation of buccoadhesive propranolol hydrochloride tablet formulations: effect of fillers

Farmaco. 2004 Feb;59(2):155-61. doi: 10.1016/j.farmac.2003.11.011.

Abstract

The buccal mucosa has been investigated for local and systemic delivery of therapeutic peptides and other drugs that are subjected to first-pass metabolism or are unstable within the rest of the gastrointestinal tract. Propranolol hydrochloride (propranolol HCl) is subjected to first-pass effect, therefore formulation of buccal-adhesive dosage form can circumvent this effect. The effect of lactose (a soluble excipient) and dicalcium phosphate (DCP) (an insoluble excipient) on dissolution rate, kinetic of release and adhesion force of buccal-adhesive tablets of propranolol HCl were evaluated. Each tablet composed of 80 mg propranolol HCl, 80 mg hydroxypropylmethylcellulose (HPMC) K4M, polycarbophil AA1 and lactose or DCP with different ratios. The results showed that the presence of the fillers increased dissolution rate of the drug. The release data also showed that the effect of lactose on the dissolution rate was greater than the DCP. Kinetic release of propranolol HCl from buccal-adhesive matrices was affected by the different ratios of polymers and fillers. The fillers reduced the bioadhesion force and this effect was more considerable in formulation containing DCP. In order to determine the mode of release, the data were analyzed based on the equation Q =kt(n). The results showed that an increase in the concentration of HPMC K4M resulted in a reduction in the value of n. The value of n was not significantly affected by an increase in the concentration of lactose or DCP. The values of n in this study were calculated to be between 0.461 and 0.619, indicating both diffusional release and erosional mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins
  • Adhesives
  • Adrenergic beta-Antagonists / administration & dosage*
  • Algorithms
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Excipients
  • Kinetics
  • Lactose / analogs & derivatives*
  • Methylcellulose / analogs & derivatives*
  • Mouth Mucosa / metabolism*
  • Nephelometry and Turbidimetry
  • Oxazines
  • Propranolol / administration & dosage*
  • Solubility
  • Tablets

Substances

  • Acrylic Resins
  • Adhesives
  • Adrenergic beta-Antagonists
  • Delayed-Action Preparations
  • Excipients
  • Oxazines
  • Tablets
  • calcium polycarbophil
  • Methylcellulose
  • MK 458
  • Propranolol
  • Lactose