Spread the love


| Format: Ms Word | 1-5 Chapters | Table of Content|


Study Level: BTech, BSc, BEng, BA, HND, ND or NCE

Amount: ₦3,000.00


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). Though modified release dosage forms are of much advantage in providing prolonged therapeutic action, they are not applicable to all drugs and treatment of short term disease conditions. Modification of drug release is usually achieved by the use of physical or chemical barriers (Yihong and Zhou, 2011), which can be controlled or sustained over time. To build the barrier into per oral dosage forms, ion exchange resins; microencapsulation; coatings; waxes; plastic matrices and polymeric materials have been used. The polymers used are usually inert, hydrophobic or hydrophilic (swellable) in nature (Nokhodchi et al., 2012) with the drug either dispersed in a polymer matrix or enclosed in a polymer membrane.


For the development of matrix systems, hydrophobic and hydrophilic polymers or both are used. Hydrophobic polymers such as ethyl cellulose, polyethylene and polypropylene when used release the drug via diffusion following Higuchi model whereas hydrophilic polymers like methyl cellulose, (MC) hydroxyl propyl cellulose (HPC); hydroxyl methyl propyl cellulose (HPMC) and the poly methyl acrylates e.g. Eudragit RS and RL release the drug by Case II transport or by a combination of Case II transport and Fickian diffusion (Perrie and Rades, 2010). Apart from the synthetic and semi synthetic polymers, hydrophilic natural polymers obtained from plants have also been used in modifying drug release. For example, guar gum has been useful in targeting drug delivery to the colon (Krishnaiah et al., 2002). A combination of natural and semi synthetic polymers, Khaya senegalensis gum (KSG) and sodium carboxymethyl cellulose (SCMC) have also released drug via fickian diffusion and case II transport (Mahmud et al., 2015). For the purpose of developing reservoir systems ethyl cellulose; Eudragit RS and RL are used as film formers. In addition, hydrophilic polymers have also been used though there is the risk of dose dumping as concern for this type of coats (Verhoeven, 2008). Polylactides and copolymers of lactic and glycolic acids are employed in the development of bioerodable matrix systems which release drug via matrix erosion.


Mucilages are produced via normal physiological process during metabolism within the cell (intracellular formation) without any injury to the plant (Qadry and Shah, 2008). Mucilages usually are composed of several sugar monomers and do not dissolve but form slimy mass in water. They are also precipitated by organic solvents. Generally, mucilages are plant hydrocolloids that on hydrolysis yield mixtures of sugars and uronic acids (Pritam and Harshal, 2014). Several findings on mucilage have shown that they contain polysaccharides with different components for example, Aloe vera gel contains acetylated mannan, galactan, arabinan and glucoronic acid, while Hibiscus mucilage contains L- rhamnose, D-galactose, D-galacturonic acid and D-glucoronic acid (Avinash et al., 2013). Mucilage from seeds of Ziziphus mauritiana-Jujube contains carbohydrate, reducing sugar and amino acid. Trigonella foenum-graceum (Fenugreek) in its seeds contains a high concentration of mucilage that is very viscous and comprises sugars of mannose, galactose and xylose types (Pritam and Harshal, 2014). Mucilage are produced from different sources and classified based on their sources. They can be obtained from plant seed (Cassia fistula), bark and fruit (Jujube, Okro) and also from plant leaves e.g. Adansonia digitata and Aloe vera


Adansonia digitata L belongs to the Family Bombacaceae/ Malvaceae. It has several names in English attributed to its physical appearance such as monkey bread (fruit pulp); dead rat (hanging fruit capsule); or upside down (root like branches) tree and African Baobab. In Arabic, it is called Buhibab (Diop et al., 2005 cited in Viljoen (2011) meaning fruit with many seeds. Though uncertain but this is thought to be the origin of the name ‗Baobab‘ in English. In Hausa, it is popularly known as ―Kuka and ―Igiose in Yoruba. It is found in the hot dry savannahs of sub-saharan Africa. It also grows in populated regions as a result secondary cultivation. Of the eight specie of Adansonia, A. digitata is the only one native to mainland Africa. It is a majestic plant and the largest succulent plant in the world with a height of 23 m and 10-12 m in diameter (Wicken, 1982; Chadare et al., 2009). The massive deciduous tree easily distinguished by its giant size and huge bottle like trunk looks swollen with short, stout tortuous branches and a thin canopy. It flowers between October and December (Watson, 2007). The flowers are prone to pollination by bats, insects and wind and rarely have a life span of a day (Ebert et al., 2002; Sidibe and Williams (2002). The ever green leaves are simple and digitalised with five leaflets on each leaf hence the nomenclature ―digitalis‖. The leaves are shed during the early dry season and appear after flowering. Some of the plants produce leaves for only 3 months in a year and during the remaining year physiological processes in the trunk and branches continues utilizing water stored in its large trunk (Gebauer et al., 2002). This hollow trunk acts as a reservoir for the plant during drought because of its high water holding capacity. The tree is known to have a life span of several hundred years and it is resistant to fire. Scientists estimated that it takes a Baobab tree between 8 and 23 years before it can produce seeds and after maturity ( > 60 years) it produces 160 -250 seeds per annum (UNCTAD, 2005). The seeds are contained in a large egg like velvety hairy fruit capsule (Wickens, 1982). The seed, fruit and pulp have gained commercial interest internationally, providing an export means where the plant is cultivated hence increase pressure on the species (Sidibe and Williams, 2002). Assogdadjo et al (2005) noted that fruiting and quantity of seed is affected by soil type and it‘s mineral. The root system is shallow but spreads widely underground further than the height of the tree hence ability to survive in dry climate and a provision for water uptake during the heavy infrequent rains. Adansonia digitata is found to be among the most effective plants that prevent water loss. Though not widely cultivated, it has been used by humans for multiple purposes as food or medicine (Ebert et al., 2002). As food in Northern Nigeria, the dried leaves are used in the preparation of soup called ―kuka‖. Its high thickening effect makes a little sprinkle sufficient for a large family. Because of its medicinal uses, it is referred to as the small pharmacy or chemist tree for the reason that all of its part including the leaves, bark, fruits and seeds are either useful as food or medicine (Etkin and Foss (1982) cited in De Caluwe et al., 2010). This could be due to the presence of bioactive compounds like terpenes, saponins, and tannins (Ramadan, 1993). The leaves have been used in treatment of fever, urinary tract infection, internal pains, otitis media, insect bites and as a guinea worm repellent. In addition to this, it has astringent property and has also been used to check excessive sweating. When dried, the leaves are used to repel insects. The oil is used in the treatment of diarrhoea and hiccough. The fruit paste is used for swollen joint pains.. Baobab has been accepted by the Food and Drug Administration Agency as a food ingredient in the US (Addy, 2009). The plant fruit pulp due to its traditional application in cosmetic, nutrition and medicine has been approved for importation into the EU (Buchmann et al., 2010). Claims of antiviral, antibacterial and nutritional properties of its various parts have been scientifically investigated (Viljoen, 2011) and are promising.

Plate I: A cluster of Adansonia digitata trees around a settlement

Plate II: Powdered Adansonia digitata leaves

1.4.1 Composition of Adansonia digitata

Baobab leaves are rich in good quality proteins, essential amino acids; minerals and vitamin A and have antioxidant activity. The amount of protein found by Yazzie et al (1994), cited in De Caluwe et al., (2010) constitutes 10.6 % with all common amino acids represented in different amounts. In terms of mineral composition, the leaves, contain more of iron and than calcium but when grown on alkaline soil, the leaves contain a high content of calcium. Adansonin, an alkaloid is said to be present in the leaves but this is yet confirmed in the Nigerian variety (Adegoke et al., 1968). Other components such as tannins, potassium tartarate, catechins and flavonic pigments were also reported to be present (Burkill, 1985). Carbohydrate is said to be the chief component of the leaves with about 60-70 %w/w followed by protein 13-15 % and lastly 4-6 % of fat and also 11 % fibre and 16 % ash. In addition, 7 to 10 % of the dry matter of leaves is mucilage (Woolfe et al, 1997; Diop et al., 2005 cited in De Caluwe et al (2010).

1.4.2 Mucilage composition

Of the few research works carried out on the mucilage, Mark et al (1977) reported that Adansonia digitata mucilage is acidic and contains glucose, rhamnose, galactose, galactoronic and glucoronic acids. The mucilage is also viscous at concentrations of 0.5 to 1.0 % w/v which is highest at neutral pH and can be lost when heated; nonetheless it remains a great soup thickener. Burkill (1985) further added that the mucilage is rich in uronic acids, rhamnose and other sugars. Adansonia digitata contains in the crude and purified mucilage a high content of protein and mineral, a very small proportion of neutral sugars rhamnose and galactose and also a high proportion of uronic acid derived from galacturonic and glucoronic acid. Baobab mucilage is further classified as a galacturonorhamnan polysaccharide which is acidic due to its high content of uronic acid (Sidibe and Williams, 2002).


1.5.1 Metoprolol tartarate

Metoprolol tartarate (MPT) is a cardio selective beta blocker classified under the Biopharmaceutical Classification System (BSC) as a Class I drug due to its high solubility and high permeability across epithelial membranes (Ashford, 2007). It is rapidly absorbed along the GIT and present good bioavailability unless it forms complexes or undergoes pre-systemic clearance where it shows incomplete bioavailability of about 50 % (Klein and Dressman, 2006). A peak plasma concentration is reached between 1-2 hours of administration of a single dose of MPT and further eliminated within 3 to 4 hours. This necessitates frequent administration of the drug for up to 4 times daily depending on the intent of treatment (Angina pectoris & Hypertension). The frequent dosing thus produces troughs and peaks in the plasma concentration-time curve, inconveniences in dosing and possible side effect plus unintended omission of doses. The existence of a well defined relationship between plasma concentration and the beta blocking effect has been well documented where different types of controlled release formulations improved the clinical quality of MPT (Verhoeven, 2008a; Klein and Dressman, 2006). These reasons account for the choice of MPT for remodelling into a modified prolonged release formulation using purified natural mucilage obtained from the leaves of Adansonia digitata plant as matrix former.


Drug delivery dosage forms control the pharmacological effect of the drug by influencing pharmacokinetics, site of action, duration of action, release rate and possibly side effects. However, an ideal drug delivery dosage form should deliver the drug at its appropriate site of action for the required duration with its concentration kept within the therapeutic range to produce maximum therapeutic response. Though, this can be achieved by conventional dosage forms for a short period, it requires repeated administration to maintain the levels which may eventually lead to peaks and troughs in the plasma concentration curve with increased drug toxicity and reduced compliance. Modification of conventional drug delivery systems are geared to the formulation of an extended/prolonged, slow release dosage form which will improve its performance such as release over a prolonged period of time or at the appropriate site in a desired concentration, keeping it within the therapeutic range and or providing maximum distribution within an organ, tissue, cell or cellular organelle. These modifications are achieved by the use of synthetic and semi synthetic polymers. Over the years, a number of natural polymers have been investigated for such purpose especially in India due to their appealing characteristics and besides, it reduces cost and problems associated with importation of the synthetic polymers. Plant derived polymers have been useful in pharmaceutical applications due to their appealing characteristics. They are relatively less toxic, non irritant, biocompatible, biodegradable and easily go into chemical reaction. They are also inexpensive, abundant and available. These appealing characteristics that plant gums and mucilages possess have enabled them to become modified to meet the requirements of drug delivery systems and as such are able to compete with the synthetic excipient available in the market (Bhardwaj et al., 2000). Amelia et al (2010) and Shyale et al (2013) have advocated the use of natural polymers as replacement for synthetic polymers which are expensive, take a long time to develop; relatively toxic and may pose some environmental concerns. Many natural polymeric materials including gums, resins and mucilages have been successfully used in modified release dosage forms e.g. guar gum, pectin, sesbania gum, mucilage from pods of Hibiscus esculenta, seed gum of tamarind, copal gum and gum dammar (Efentakis et al., 2001). Their suitability as buccal films (Pandrey et al., 2004) and in formulations such as matrix controlled systems and delayed release systems (Alonso et al., 2009) have been explored. Furthermore, disintegrant action of the dried mucilage powder isolated from aerial part of Salicornia fruitosa (Rishabha et al., 2011) and the binder and muco-adhesive action of Caesalpinia pulcherrim seed mucilage on tablet formulations (Gangurde et al., 2012) have also been demonstrated. Within the West African region, several works have also reported the potential applications of natural polymers in drug delivery systems. For example, Ofori- Kwakye et al (2015) demonstrated the usefulness of natural gums in extended release dosage forms which compared favourably with HPMC while Kamalakkannan et al (2015) found Kodangogu gum promising in prolonged release formulations. In Nigeria, a number of researches have also been carried out on natural plant polymers. Odeku et al (2005) investigated the use of Khaya and Albizia gums as compression coatings for colon specific drug delivery systems. Again, Odeku et al (2006) reported that khaya gum matrices possess acceptable mechanical and drug release properties. Several studies have also been carried out in Zaria exploring the potential use of Khaya senegalensis gum as modified drug release matrices (Mahmud et al., 2008, 2015; Oyi et al., 2010; Olayemi et al., 2010). Abdurrahman et al (2015) derived a swellable polymer from cashew gum that may have potential for use in controlling drug release in pharmaceutical formulations Adansonia digitata has been reported to have medicinal and nutritional properties (Viljoen et al., 2011). In Northern Nigeria, Adansonia digitata (AD) leaves is used for soup while the pulp is used as juice. The presence of mucilage in its leaves makes it slippery and gives it ability to swell. These physically observed properties when researched into may provide potentials for its use as a coating agent or a gelling matrix former and hence ability to prolong drug release. The only previous study on the pharmaceutical application of mucilage from the leaves of this plant is that of Shayle et al (2013) who showed that it has a potential as a suspending agent in paracetamol suspension. Until now, mucilage from the leaves of Adansonia digitata has not been explored for use as matrices in tablet formulations.


Adansonia digitata leaves are abundantly available in northern Nigeria and currently not employed as a pharmaceutical excipient. It requires little capital to process it into pharmaceutical acceptable raw material hence will be a cheaper alternative to imported gums and other polymers. Furthermore, it will reduce the cost of medication, importation and importation problems associated with the use of synthetic polymers.

A positive outcome of this study will encourage the cultivation of Adansonia digitata plants. This will create job opportunities for the inhabitants of the areas and improve their economic base. Sandip et al (2012) reported that the suitability of natural gums as excipient have encouraged production of plants like guar gum and tragacanth by governments in developing countries like India. Adansonia digitata mucilage can be fully characterized and its potentials as pharmaceutical excipient may be discovered and perhaps it may become a mainstay polymer in pharmaceutical industries in Nigeria.


  • Null Hypothesis: Adansonia digitata mucilage (ADM) does not possess characteristics required for the formulation of a prolonged drug release tablet dosage form.
  • Alternate Hypothesis: Adansonia digitata mucilage (ADM) is a useful natural polymer matrix in the formulation of prolonged drug release oral tablet dosage forms.

1.9 AIM

Development of a pharmaceutical grade Adansonia digitata mucilage as excipient in prolonged release oral tablet dosage formulations.

1.9.1 Specific objectives

Specific objectives towards achievement of this goal are:

  1. Collection, authentication, purification and phytochemical screening of mucilages from Adansonia digitata leaves using standard procedures.
  2. Carry out phytochemical screening to determine the purity of the extract.
  3. Characterization of the physicochemical properties of purified mucilage powder such as morphology, colour pH, moisture content, moisture sorption and relative humidity, viscosity, chemical compositions etc, using appropriate techniques and instruments.
  4. Investigation of the binding ability of ADM by formulation of immediate release tablets via wet granulation method of tablet manufacture and also evaluation of produced granules and corresponding tablets.
  5. Formulation of prolonged release tablets by matrix technique using ADM and comparison with formulations of synthetic polymer HPMC of similar viscosity grade.
  6. Evaluation of the formulated tablets using both compendia and non compendia tests such disintegration, in vivo dissolution profiles, liquid uptake, erosion and swelling parameters.
  7. Perform in vivo assessment of the formulation in dogs relative to a marketed product
  8. Carry out thermo analysis and compatibility studies of the formulations using Differential Scanning Calorimeter (DSC).
  9. Use statistical tests and mathematical models to evaluate the suitability of ADM as a prolonged drug release excipient.



Account Number: 0709546102

Access Bank: Savings
Account Name: Emmanuel Idorenyin Samuel.


Leave a Reply

Your email address will not be published. Required fields are marked *