Kinetic release of theophylline from hydrophilic swellable matrices.
The objective of this research was to evaluate the effect of hydroxypropylmethylcellulose (HPMC; Methocel K4M Premium) level and type of excipient on theophylline release and to attempt to predict the drug release from hydrophilic swellable matrices. Formulations containing theophylline anhydrous (10% w/w), Methocel K4M Premium (10%, 30%, and 40% w/w), different diluents (Lactose Fast Flo, Avicel PH-101, and Emcompress), and magnesium stearate (0.75% w/w) were prepared by direct compression at a target weight of 450 mg +/- 5% and target hardness of 7 kp to 10 kp. It was found that, as the percentage of polymer in all formulations increased from 10% to 30% or 40%, the drug release decreased. However, there was no significant difference in drug release between formulations containing 30% polymer and formulations containing 40% polymer. At low levels of polymer, the drug release is controlled by the type of diluent used. Avicel PH-101 formulation gave the highest release, while its corresponding Emcompress formulation gave the lowest release. Formulations containing 30% or 40% polymer gave the same release profiles irrespective of the type of diluent used. In all cases, replacement of a portion of Methocel K4M Premium with any diluent resulted in increase of theophylline release. In addition, this investigation demonstrated that the drug release from hydrophilic swellable matrices can be predicted using only a minimum number of experiments.
Vargas
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School of Pharmacy, University of Puerto Rico, San Juan 00936-5067.
Ghaly
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D000284:Administration, Oral; D005079:Excipients; D007785:Lactose / Q000031:analogs & derivatives* / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008962:Models, Theoretical; D010078:Oxazines; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D012997:Solvents; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013806:Theophylline / Q000493:pharmacokinetics*; D013997:Time Factors
D005079:Excipients; D010078:Oxazines; D011108:Polymers; D012997:Solvents; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; D008747:Methylcellulose; C071191:MK 458; D013806:Theophylline; D007785:Lactose