THE USE OF A NOVEL POLYMER FROM THE STEM BARK OF CISSUS POPULNEA IN THE FORMULATION OF CONTROLLED RELEASE MATRIX TARLETS

THE USE OF A NOVEL POLYMER FROM THE STEM BARK OF CISSUS POPULNEA IN THE FORMULATION OF CONTROLLED RELEASE MATRIX TARLETS

Abstract:

Investigations were undertaken on the physico-chemical, microbiological and controlledrelease properties of cissus populnea polymer (CPP), a hydrocolloid polymer obtained from the stem bark of Cissus populnea amplidaceac (vitaccae). which grows wild in many parts of Nigeria. The mucilage is widely used for preparing edible thick viscous soup (“draw soup”). Theophylline and Potassium chloride were used as drug models for poorly water soluble and very water soluble drugs respectively in evaluating the controlled-release properties of CPP. A spectrophotometric method and a flame photometric method were used in assaying the quantities of theophylline and potassium chloride respectively that were released from the formulated matrices. Thermal analysis using the Perkin – Elmer Differential Scanning Calorimeter was employed for investigating interactions between the CPP and these drugs as well as their thermal properties. Erosion and swelling of tablets with time were measured in different dissolution media to establish the conditions for “low” and “high” erosion and swelling used in the factorial design studies. CPP was seen to be insoluble in aqueous medium but swells into a viscous gel which provides a barrier to drug diffusion from the tablets, thus providing a means of prolonging drug release for hours. The controlled-release of theophylline and potassium chloride from CPP matrices were longer and more linear than from methocel/HPMC, CAP, lactose and dicalcium phosphate matrices. Thermal studies using DSC showed that CPP did not form any complex with either of these drugs, consequently no interference with the therapeutic effects of the drugs will occur. “Once-and twicedaily” theophylline tablets were formulated with the CPP. The “twice-daily” formulation showed chemical and release rate stabilities at room temperature, but these parameters were affected by higher temperatures and humidities. Like xanthan gum investigated by other workers, CPP’s prolongation of drug release was dependent on polymer concentration, but changes in pH, ionic strength and surfactant concentration did not significantly alter the release rate as shown by ANOVA and t-test. However other factors such as compression pressure, dose content and agitation speed could affect the release rate. The correlation coefficients for various release models showed that CPP gave zero-order release kinetics for most test conditions. From factorial design experiments using “steady” and “nonsteady” states it is evident that erosion is the main mechanism of theophylline release from CPP matrices while swelling (acting independent of erosion) imparts linearity to the release profile. Granulation increased the prolongation and linearity of drug release from CPP matrices, whereas magnesium stearate exhibited an optimum concentration for enhancing the prolongation of drug release from CPP matrices, below and above which drug release rate increased. These two factors also affected the thermal intrinsic properties of theophylline -CPP mixtures. Computer pharmacokinetic simulations of the formulated products showed that the 22 hour release form of the “once-daily” tablets gave the best plateau in plasma drug level after 5 multiple doses, while the “twice – daily” tablets showed a reduced Cmax and a much longer tmax than an equivalent immediate release formulation. Also the AUCs of the “twice-daily” and immediate release products were identical, showing that the “twice-daily” formulation would perform successfully in-vivo. The “once-daily” theophylline tablets formulated with CPP appear to be more satisfactory than the commercially approved products studied. The microbiological studies on CPP (as a substance from vegetable source) gave an acceptable limit of microbial counts and absence of pathogens. CPP’s low water activity led to no microbial growth during the study period of 3 months. CPP could be a suitable substitute to presently used hydrocolloids and could greatly improve the in-vitro and in-vivo performances of many matrix controlled-release tablets in the market.

THE USE OF A NOVEL POLYMER FROM THE STEM BARK OF CISSUS POPULNEA IN THE FORMULATION OF CONTROLLED RELEASE MATRIX TARLETS