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
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Date
1997-07
Authors
IBRAHIM, MUSA ANDREW
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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.
Description
A THESIS SUBMITTED TO THE POSTGRADUATE SCHOOL
AHMADU BELLO UNIVERSITY ZARIA
IN FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF
Ph.D PHARMACEUTICS
Keywords
USE,, NOVEL,, POLYMER,, STEM,, BARK,, CISSUS,, POPULNEA,, FORMULATION,, CONTROLLED,, RELEASE,, MATRIX,, TARLETS