Preparation of Losartan Potassium Controlled Release Matrices and In-Vitro Investigation Using Rate Controlling Agents

Abstract

Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.

Preparation and In Vitro Evaluation of Controlled-Release Matrices of Losartan Potassium Using Ethocel Grade 10 and Carbopol 934P NF as Rate-Controlling Polymers

“…Till now, several polymers have been tested for their effects on losartan potassium release. Among them, Eudragit, ethylcellulose, and Kollidon [ 10 , 11 , 12 ] were found to be effective when included in sustained-release formulations. Additionally, a recent study assessed the properties of losartan potassium tablets prepared by adding ethylcellulose Ethocel grade 100 and Carbopol 934P NF [ 10 ].…”

“…Percent friability was calculated as previously described [ 10 ]. Finally, 20 randomly selected matrices were weighed by a digital electronic balance (Shimadzu, Kyoto, Japan).…”

“…The dissolution rates were compared by applying difference and similarity factors f1 and f2, respectively [ 10 ].…”

“…It is well known that sustained-release forms of losartan potassium may help in reducing side effects such as migraine, pancreatitis, or hepatotoxicity [ 8 ]. Therefore, several losartan potassium sustained-release matrices have been designed, often prepared by the direct compression method by using polymers such as Eudragit RLPO, Eudragit RSPO, and ethylcellulose, either alone or associated with each other, observing an extension of the drug release up to 12 h when using Eudragit polymers in combination with ethylcellulose [ 10 , 11 ], following an anomalous non-Fickian drug release mechanism [ 11 ]. Similarly, other authors devised and prepared losartan potassium sustained release matrix tablets by the direct compression method using Kollidon SR [ 12 ] and methylcellulose [ 13 ] as rate-retarding polymers.…”

“…Controlled-release tablets of losartan potassium were also developed by using Ethocel 100 Premium and Ethocel 100 FP Premium, evidencing that the latter extended the drug release rate due to the smaller size of its particle if compared to Ethocel 100 Premium [ 15 ]. The incorporation of losartan potassium in a matrix consisting of Ethocel grade 100 and Carbopol was found to further extend the drug release [ 10 ].…”