Physical and chemical properties of rapid-release systems prepared by a thermal granulation technique

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Koleng, John Joseph

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The physicochemical properties of rapid-release drug delivery systems prepared by the thermal granulation of fine powder pharmaceutical compositions using hot-melt extrusion (HME) were investigated. Thermal processing represents an alternative production technique to the traditional methods of wet granulation or dry granulation. Acetaminophen (APAP) was thermally granulated with polyethylene glycol (PEG) or poloxamer. APAP was demonstrated to be thermally stable. The molecular weight, dissolution rate, and aqueous viscosity of the thermal binders influenced APAP dissolution. Additionally, APAP dissolution was dependent upon the thermal binder concentration and the properties of the filler excipient. The most rapid dissolution was obtained with 15% polyethylene glycol and soluble filler excipients. viii APAP dissolution was more rapid from a thermally granulated composition than from a wet granulated formulation. Ibuprofen (IBU) was thermally granulated using the drug as a melt binder. IBU stability was demonstrated to be dependent upon temperature and duration of exposure. Granule particle size, tablet hardness, and filler excipient influenced the dissolution of IBU. Thermally granulated IBU tablets were prepared that provided similar dissolution rates to commercially available products. Tocofersolan (TPGS) was used to thermally granulate phenylbutazone (PBZ) and diphenhydramine HCl (DPH). PBZ was oxidized by TPGS, and oxidation was dependent upon TPGS concentration, temperature, and duration of exposure. Ascorbic acid was found to inhibit the TPGS-mediated oxidation of PBZ. DPH did not exhibit oxidation in the presence of TPGS. Although the thermal binder and the addition of ascorbic acid influenced PBZ dissolution, greater than 80% dissolution was obtained at 15 minutes. DPH dissolution from tablets containing either PEG or TPGS was complete within 10 minutes. HME was successfully employed to thermally granulate rapid-release systems. The thermal stability and compatibility of the drug and excipients must be evaluated to determine the appropriate thermal binder and extrusion conditions. Thermal binder concentration, granule particle size, and functional excipients must be optimized to provide the desired physical properties of the drug product



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