Evaluation of the Gum from Hakea gibbosa as a Sustained-Release and Mucoadhesive Component in Buccal Tablets

• Published in: Pharmaceutical development and technology Vol. 4; no. 3; pp. 347 - 358
• Main Authors: Alur, Hemant H., Pather, S. Indiran, Mitra, Ashim K., Johnston, Thomas P.
• Format: Journal Article
• Language: English
• Published: New York, NY Informa UK Ltd 1999; Taylor & Francis; Informa Healthcare
• Subjects: Adhesives; Administration, Oral; Biological and medical sciences; Buccal mucosa; Buccal tablets; Calorimetry, Differential Scanning; Cheek; Chlorpheniramine - administration & dosage; Chlorpheniramine maleate; Delayed-Action Preparations; Drug Compounding; Excipients - chemistry; General pharmacology; Histamine and antagonists. Allergy; Histamine H2 Antagonists - administration & dosage; Medical sciences; Models, Theoretical; Mouth Mucosa - metabolism; Mucoadhesion; Non-Fickian diffusion; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plant Gums; Polysaccharides - chemistry; Powders; Solubility; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Sustained-release; Tablets; Pharmaceutical technology; Granulation; Controlled release form; Mucosa; Proteaceae; Direct compression; Antihistaminic; Dissolution; In vitro; Modeling; Oral cavity; Dicotyledones; Angiospermae; Dosage form; Active ingredient; Spermatophyta; Tablet; Chlorphenamine; Diffusion; Bioadhesive system; Gum; Release
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1081/PDT-100101370

The objective of this paper was to evaluate the mucoadhesive and sustained-release properties of the water-soluble gum obtained from Hakea gibbosa (hakea), for the formulation of buccal tablets. Flat-faced tablets containing hakea were formulated using chlorpheniramine maleate (CPM) as a model drug. Two types of tablets were prepared: uncoated tablets (type I) and tablets in which all but one face of the type I tablet was coated with hydrogenated castor oil (Cutina) using a compression coating technique (type II). In an attempt to explain the observed sustained-release effect, the potential for a chemical interaction between hakea and CPM was evaluated by FTIR, differential scanning calorimetry (DSC), UV spectroscopy, and acid-base titrations. Mathematical modeling of the CPM release data was developed to elucidate the mechanism of drug release. The mucoadhesive strength was evaluated by quantitating the force of detachment. Finally, the rates of water uptake and erosion were determined for the buccal tablets. The time required for 90% of the CPM to be released in vitro (t90%) was used as a basis for comparison. For formulations that did not contain hakea, the t90% was 14 min for both directly compressed and wet granulated tablets, whereas the t90% for wet granulated tablets containing 2 or 32 mg hakea tablet was 36 and 165 min, respectively. Directly compressed tablets containing 2, 12, 22, and 32 mg hakea tablet displayed t90% values of 48, 120, 330, and 405 min, respectively. DSC, FTIR, UV spectroscopy and acid-base titration experiments suggested the absence of chemical interactions. The force of detachment for directly compressed and wet granulated tablets increased from 0.70 ± 0.3 to 4.08 ± 0.52 N and from 0.65 ± 0.28 to 3.94 ± 0.31 N as the amount of hakea per tablet was increased from 0 to 32 mg, respectively, at a 5 N attachment compression force. The novel natural gum, hakea, may not only be utilized to sustain the release of CPM from a unidirectional-release buccal tablet, but it also exhibited excellent mucoadhesive properties. The mechanism by which CPM release was sustained was more likely due to slow relaxation of the hydrated hakea. The mucoadhesive strength can be modulated by altering the amount of hakea in the tablet.