Influence of additives on (hydroxyethyl) methylcellulose properties: relation between gelation temperature change, compressed matrix integrity and drug release profile

Tablets comprising a compressed matrix of a methylcellulose (MC) derivative mixed with various drugs and additives show 3 distinct types of behaviour in a disintegration test: rapid disintegration (D), gradual attrition (A) and maintenance of integrity (ND). Kinetic studies showed that ND matrices gave drug release related to square-root of time (i.e. matrix diffusional model) whereas a typical A matrix (salicylic acid-MC) deviated positively but observed the Hixson-Crowell cube-root equation for dissolutional control, as applicable to polyphase mixtures. In Une with these models, the matrix-controlled system was unaffected by and the dissolution one dependent on stirring conditions. For clarifying the mechanism of matrix behaviour, gelation temperature and viscosity were studied using dilute aqueous systems. Gelation temperature was raised by ND additives, salts containing large organic ions (including sodium benzoate, octanoate, salicylate, tetracaine-HCl. potassium phenoxypenicillin, chlorpheniramine maleate) thiocyanate and iodide. It was lowered by inorganic and small organic ions, lactose and some free organic acids causing A and D behaviour. The elevation, which has not hitherto been noted, is especially interesting. Intrinsic viscosity was raised by sodium salicylate and lowered by sodium chloride, the Huggins' constant being lowered by the former and raised by the latter. These gel point and viscosity changes reflect increased hydration and extension of the macromolecule chain in the former system and dehydration in the latter, such changes being associated with increased or decreased polymer cohesion in the compressed matrix.