Pharmaceutical Sciences




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.




Advancement in modern techniques in the area of synthesis of new compounds, structural modification of existing compounds and discovery of natural and combination of structurally related compounds has led to the development of a large number of drug products in a short time to combat diseases which prior to now remain impossible. The developed drugs (active ingredient) can only be clinically effective when incorporated into a suitable medium that enables for handling by the patient and proper delivery at the required site of action. This is mostly achieved by the addition of components of formulation called excipients. This medium in which the drug is incorporated and presented for handling is termed as a dosage form or drug delivery system (Perrie and Rades, 2010). Specifically, a dosage form is the physical form in which a drug is incorporated whereas a delivery system is a means by which the medicine releases the drug and delivers it at its target site (organ, tissue, cell or cellular organelle). Modification of drug delivery involves the application of changes to the already existing drugs in order to improve their stability, efficacy; drug safety and patient compliance.

Modified release dosage forms (MRDF) refer to those dosage forms whose release properties, release rate characteristics or location are chosen to achieve therapeutic or convenient objectives that conventional dosage forms cannot provide (USP, 2011). They are designed in such a way that control is taken away from the patient and somewhat away from the physician but placed in drug delivery systems. Basically these dosage types are either designed to provide prompt drug plasma levels maintained constant in the therapeutic range over a prolonged period (controlled released) or prompt drug release followed by prolonged gradual release within the therapeutic range but not maintained constant (sustained release) or releases the drug when it reaches a given location (delayed and target release) (Collett and Moreton, 2007). According to Collett and Moreton (2007), an ideal modified release dosage form is that which releases its priming dose immediately after administration in order to elicit a desired therapeutic effect and release slowly, subsequent doses so as to achieve a therapeutic plasma concentration that is not constant but maintained over a long period of time. These dosage types are formulated to:

  • Provide a prolonged plasma concentration within the therapeutic range thus preventing repeated administration of drug at different time intervals.
  • Increase patient compliance from a 2-3 times daily medication to a less frequent once daily dosing (Nokhodchi et al., 2002) most especially in chronic diseases, and
  • Minimize side effects (Hosny, 1995; Maderuelo et al., 2011 ) associated with repeated administration and fluctuations in plasma concentration and finally to deliver the drug at specified locations of the GI.

Limitations of the system include;

  • High cost of medication as compared to immediate release tablet dosage forms.
  • Unpredictable release pattern as there is no definite correlation between in vivo/in vitro release (Yao and Weiyuan, 2010).
  • Dose dumping may occur as a result of delivery system failure leading to decrease bioavailability (drug subjected to hepatic metabolism for some drugs) and increased toxicity (Nokhodchi et al., 2012).

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