Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.
Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to <30 s by addition of any of the diluents. The indication is that the inclusion of the diluents studied can be used to improve the compressibility of the otherwise poorly compressible matrix granules. Based on the flowability, compressibility, and disintegration data, carnuba wax proved most promising in the melt granulation of the test drug for sustained release applications.
Uhumwangho
M U
MU
Department of Pharmaceutics, University of Benin, Benin City, Nigeria. mike2003u@yahoo.com
Okor
R S
RS
D000082:Acetaminophen / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000737:chemistry*; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D012212:Rheology; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength; D013997:Time Factors; D014885:Waxes / Q000737:chemistry*
D018712:Analgesics, Non-Narcotic; D005079:Excipients; D013607:Tablets; D014885:Waxes; D000082:Acetaminophen; D002482:Cellulose; D007785:Lactose; C109691:microcrystalline cellulose