FORMULATION STUDIES OF TABLETS CONTAINING ADANSONIA DIGITATA L. MUCILAGE AS MATRIX FORMER
FORMULATION STUDIES OF TABLETS CONTAINING ADANSONIA DIGITATA L. MUCILAGE AS MATRIX FORMER
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Date
2016-02
Authors
MAHMUD, HALIMA SA’ADIYA
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Abstract
The aim of this study was to investigate the ability of Adansonia digitata mucilage (ADM), a
hydrophilic plant polymeric material to prolong the release of Metoprolol tartarate (MPT) from
matrix tablet formulations compared with semi -synthetic polymer-HPMC60SH4000 matrices.
Phytochemical screening and physicochemical characterization of the extracted ADM was
performed using standard and official procedures. Physicochemical tests such as simple
(quantitative yield, aqueous solubility and pH tests) and analytical techniques ( viscosity tests by
rotational viscometer, elemental analysis by Carbon, Hydrogen, Nitrogen (CHN) method, thermo
analysis using Differential Scanning Calorimeter (DSC), functional groups determination via
Attenuated Total Reflectance Fourier Infra Red (ATR-FTIR) and structure elucidation by
Carbon -13 Nuclear Magnetic Resonance (NMR). Particle characterization via Qicpic and
Scanning Electron Microscopy (SEM), moisture content and sorption determination by Karl
Fischer and Dynamic vapour sorption (DVS) techniques.
Phytochemical screening as well as thermo analysis revealed a level of purity in the extraction
process. The mildly acidic mucilage had a low yield (3.5%) and high viscosity that increased
with increasing mucilage concentration. Additionally, it was characterized by glass transition and
melting temperatures of 74 °C and 173 °C respectively. Finger prints of functional groups
revealed azo aromatic groups and other chemical constituents of sugars including glucose,
galactose, rhamnose and sugar acids identified by NMR.
To assess its ability to cohere powdered drug particles, ADM was used as a binder in
concentrations of 0.33 % with addition of surfactant, 0.5 % and 1.0 % w/w in the formulation of
immediate release MPT tablets by wet granulation method of tablet manufacture. The granule
micrometrics and tablet properties evaluated revealed that 0.5% w/w batch had a better binder spread on powdered mix bed that translated into granules with good flow and particle size
distribution (PSD) which corroborated well with SEM imaging as well as granule shapes and the
corresponding tablets delivered MPT tablets with acceptable strength while DT did not differ
significantly when surfactant was added.
Furthermore, the matrix forming potential of ADM for prolonged release action was investigated
in MPT tablets compressed by direct compression in the ratios of 50/50 and 20/80 of drug
polymer concentrations. The in vitro drug release in acid (pH 1.0) and phosphate (pH 6.8)
buffers, swelling and liquid uptake studies, drug release kinetics and mechanism were studied
while in vivo studies was carried out on 20/80 ADM matrices in dogs and the pharmacokinetic
parameters relative to a marketed formulation of same strength; Slow-Lopressor® Divitab 200
mg was obtained. The matrix tablets produced had acceptable tablet quality and the release
profiles of the 20/80 matrices displayed a linear and pH independent release while burst effect
was only observed in the tablets with low HPMC concentration. The matrix integrity was
maintained throughout in vitro dissolution for ADM matrices as a result of better gel strength.
The drug release kinetics followed Higuchi model while the mechanism was anomalous Fickian
diffusion and super case II transport as a result of the swelling effects of the polymer. Similarity
factor (f2) showed that the in vitro release profiles of the 50/50 and 20/80 formulations were
similar in both dissolution media used. Besides, statistically, in vitro MPT release from ADM
and HPMC60SH4000 (20/80 drug: polymer) and in vivo profiles after oral administration of the test
formulations to dogs did not differ significantly from the reference marketed sustained release
product (P > 0.05). In conclusion, Adansonia digitata mucilage was found to be an excellent
matrix former in prolonged release tablets of MPT that was comparable to semi- synthetic
polymer of high viscosity, HPMC60SH4000.
Description
A THESIS SUBMITTED TO THE SCHOOL OF POSTGRADUATE STUDIES,
AHMADU BELLO UNIVERSITY, ZARIA
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF
DOCTOR OF PHILOSOPHY IN PHARMACEUTICS
DEPARTMENT OF PHARMACEUTICS AND PHARMACEUTICAL MICROBIOLOGY
FACULTY OF PHARMACEUTICAL SCIENCES
AHMADU BELLO UNIVERSITY, ZARIA
NIGERIA.
Keywords
FORMULATION STUDIES,, TABLETS CONTAINING ADANSONIA DIGITATA L,, MUCILAGE,, MATRIX FORMER,