Browsing by Author "Belete, Anteneh(PhD)"

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    Enhancing the Dissolution and Sustaining the Release of Diclofenac Sodium Using the Method Liquisolid Technology
    (Addis Ababa University, 2014-05) Tesfaye, Lidia; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    Various methods of modifying solubility and dissolution properties of drugs have been developed over the years. Methods such as liquisolid technology, which can be used to enhance or sustain dissolution, have raised a lot of interest in many researchers. In this study different liquisolid compacts of diclofenac sodium containing either propylene glycol or polyethylene glycol 400 for the enhanced dissolution preparations; and Polysorbate 80 as a non-volatile solvent for sustained preparation were prepared using a mathematical model for calculating required quantities of powder and liquid ingredients to produce acceptably flowable and compressible admixture. Microcrystalline cellulose, colloidal silica and sodium starch glycolate were employed as carrier, coating material and disintegrant, respectively. Formulation of liquisolid compacts having various ratio of carrier to coating material (ranging from 10 to 30) and 50 to 70% concentration of liquid medication (drug:non-volatile solvent) were prepared and evaluated for their powder, tablet property and drug release profile. The liquisolid compacts demonstrate considerably higher dissolution rate than marketed tablets. This was due to increased wetting properties and surface of drug available for dissolution. Also it has been shown that the fraction of molecularly dispersed drug in the liquid medication of liquisolid system was directly proportional to the dissolution rate and the percentage drug dissolved in 10 minute was correlated with solubility of the drug in different vehicle. A plot of the percentage drug dissolved against the solubility of diclofenac sodium showed that the amount of drug dissolved increased linearly with an increase in solubility of diclofenac sodium in the vehicle. Diclofenac sodium tablets prepared by liquisolid technique also showed release retardation properties. This study revealed that Polysorbate 80 and Eudragit® RL has important role in sustaining the release of drug from liquisolid matrices. It is generally proven that liquisolid technique is a promising alternative as a tool to enhance or sustain the release of diclofenac sodium. Key words: Liquisolid compact, Diclofenac Sodium, Solubility, Dissolution, Sustained release.
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    Evaluation of Binding Capacity of Gum Fraction of Local Myrrh (Commiphora myrrha Syn. C.molmol) in Granule and Tablet Formulations
    (Addis Ababa University, 2014-12) Mekonnen, Taddese; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    Evaluation of the Binding Capacity of the Gum Fraction of Local Myrrh (Commiphora myrrha Syn. C.molmol) in Granule and Tablet Formulations Taddese Mekonnen Addis Ababa University, 2012 Myrrh is an oleo-gum resin which is economically and culturally valuable product obtained from several species of the genus Commiphora. The chief source of myrrh is Commiphora myrrha (synonym C. molmol). They are important plant products used in several industries that include food, flavour, liquor and beverage, cosmetics, perfumery, pharmaceuticals and others. Gums are considered to be pathological products formed following injury to the plant or owing to unfavorable conditions. They are frequently used in pharmaceuticals as thickening, binding, emulsifying, and suspending, gelling and stabilizing agents and also used as coating materials in microencapsulation. As binders they impart adhesive qualities to the powder material by formulation of granules of the desired size, hardness, strength, friability and compressibility. In this study, the gum fraction of myrrh oleo-gum resin was extracted from local myrrh (Commiphora myrrha syn. C. molmol) and its binding capacity in granule and tablet formulations was evaluated using paracetamol as a model drug. Some physico-chemical properties of the extracted gum such as the presence of tannin and starch/dextrin, loss on drying, total ash value, pH of gum mucilage, water solubility index, swelling power, relative solubility, moisture sorption-desorption, viscosity and powder flow properties were investigated. Granules containing paracetamol were prepared using 2%, 5%, 7.5% and 10% w/w of the extracted gum and reference binders (PVP K-30 and Acacia BP) by wet granulation technique. The granules were characterized for particle size and size distribution, bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate and friability. Tablets containing paracetamol and different concentrations of binders were prepared using a single punch tablet machine at a fixed compression force. Tablets were evaluated for their weight uniformity, thickness, iv diameter, hardness (crushing strength), tensile strength, friability, disintegration time and in vitro release profile. Finally, some properties of granules and tablets prepared with the extracted gum were compared with properties of respective granules and tablets prepared using the reference binders. The results indicated that the myrrh gum exhibited good relative solubility in cold and hot water, good water solubility index, poor swelling power, acceptable moisture content, small total ash value, no tannin and starch/dextrin content, gum mucilage with acidic pH, high moisture sorption-desorption pattern, and acceptable viscosity and powder flow properties. The granules prepared with the myrrh gum and reference binders all showed good particle size and size distribution, flow and compressibility properties, and friability decreased with increasing binder concentration. All the prepared tablets passed pharmacopoeial specifications with respect to their uniformity of weight, thickness, diameter, hardness and tensile strength. However, all tablets with 2% binder concentration failed to comply with the pharmacopoeial specification for friability test (> 1%). Disintegration times of tablets were determined and only those tablets prepared with myrrh gum and acacia as binders at 10% concentrations failed to meet the British pharmacopoeia specification for disintegration (>15 min). In vitro drug release studies showed that there was a general decrease in the release rate of paracetamol from the tablets as the binder concentration increased. Tablets made with myrrh gum as binder gave higher dissolution profile than acacia and comparable profile to tablets prepared with PVP K-30. Key Word: Myrrh gum
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    Formulation and Optimization of Sustained Release Floating Matrix Tablet of Salbutamol Sulphate Using Xanthan Gum and Hydroxypropyl Methylcellulose Polymer Blend
    (Addis Ababa University, 2014-06) Yilma, Zewdu; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    Salbutamol sulphate is a directly acting sympathomimetic agent with selective action on ß2-receptors. It is used as bronchodilator in the management of disorders involving reversible airways obstruction and in chronic obstruction pulmonary diseases. Oral salbutamol sulphate has site-specific absorption in the stomach and upper part of the small intestine. Its bioavailability is about 40% due to extensive hepatic first pass metabolism, sulphonation in intestinal fluid, degradation in colon and narrow absorption window. The aim of this study was to formulate and optimize a sustained release floating tablet of salbutamol sulphate using xanthan gum (XG) and hydroxypropyl methylcellulose (HPMC) as release retarding agents and sodiumbicarbonate (NaHCO3) as floating aid in order to improve bioavailability, reduce dosing frequency, and increase patient compliance. The sustained release floating tablets of salbutamol sulphate was prepared by wet granulation technique using XG and HPMC as release retarding polymers. The effects of formulation variables: percentage of polymer (XG, HPMC, or XG/HPMC) and percentage of sodium bicarbonate on response variables: floating lag time, floating duration, cumulative release within 1 hr, and release rate were investigated. Preliminary studies revealed that the percentage of sodium bicarbonate, percentage of polymer (XG, HPMC, or XG/HPMC) significantly affected the floating lag time, cumulative release within 1 hr and release rate (P < 0.05), but not floating duration. Among the polymers used, the one with 1:3 (XG:HPMC) ratio was selected for further optimization purpose due to that it contains relatively high amount of HPMC, which has low hydration power than XG, that can release enough amount of drug in the first 1 hr which can be used as bolus dose for rapid relief of asthma. The effect of formulation variables on floating lag time was significant, but all formulations floated below 10 seconds and not considered during optimization. The effects of percentage of NaHCO3 and percentage of XG/HPMC (1:3) were studied and optimized for maximum desired output of drug release rate and cumulative release within 1 hr using central composite design statistical approach. Design-Expert 8.0.7.1 software was employed to carry out the experimental design, statistical analysis, and numerical and graphical optimization. iv Linear and quadratic models were developed as best fit models for release rate and cumulative release at 1 hr, respectively. The analysis of variance (ANOVA) of the models showed that the linear effects of both parameters were significant for the linear model of release rate; and all the linear, interaction and quadratic effects were significant for the quadratic model of cumulative release at 1 hr. The effect of percentage of XG/HPMC was more pronounced than the effect of percentage of NaHCO3 on both models. Finally, simultaneous optimization of cumulative release at 1 hr and release rate was performed and the most desirable representative optimal point was obtained to have release rate of 28.49 hr-1/2 and cumulative release at 1 hr of 24% at corresponding levels of 24.79% of XG/HPMC and 5% of NaHCO3 with desirability of 0.756. The validity of this optimal point was confirmed by the low magnitude of percent prediction error. Evaluation of the optimized formulation showed successful formulation of the floating tablets with excellent granule and tablet property. Comparison of the release profiles of three different batches of the optimized formulation by dissolution efficiency revealed that there was no statistically significant difference (p > 0.05) in release profiles of the formulations. In addition, drug release kinetics and drug release mechanism studies indicated that the optimized formulation followed Higuchi square root kinetic model with non Fickian diffusion release mechanism. In conclusion, this study has come up with an optimum formulation for the development of floating tablet of salbutamol sulphate that could remain buoyant and release the drug over a period of 12 hr in a sustained manner in vitro. Keywords: GRDFs; Floating tablet; Salbutamol sulphate; Xanthan gum; HPMC; Optimization
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    Formulation and Optimization of Taste-masked Orodispersible Tablets of Styrene- Divinyl Benzene Copolymer Complexed Metoclopramide by Sublimation Technique
    (Addis Ababa University, 2016-10) Olani, Gideon; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    Metoclopramide (MCP) is used to treat gastroparesis, by stimulating stomach activity to empty the stomach. The matter that complicates oral administration of MCP is the fact that patients with gastroparesis often have symptoms such as vomiting and nausea as well as fullness and bloating, each of which can lead to patient discomfort with or unwillingness to swallow the available oral tablet and associated water. If vomiting takes place, the amount of MCP that remains in the stomach is unknown, and the result of treatment is even less predictable. This study provides a rapidly dissolving oral MCP formulation and administration of MCP for immediate release formulation to abate the rapid onset of gastroparesis. Conventional taste masking techniques such as use of sweeteners, amino acids, flavoring agent are often unsuccessful in masking the taste of highly bitter drugs since they are overpowered by the taste of the medicine. MCP is an intensely bitter drug; hence, if it is incorporated directly into an orodispersible tablet (ODT), the main objective behind formulation of such a dosage form will definitely become futile. Hence, ion exchange resin (IER) has been used as drug carrier to mask its taste after the drug is loaded into an IER by an exchanging reaction, with the formation of drug–resin complex. Screening experiments for parameters such as: drug to resin ratio, swelling time and stirring (complexation) time were optimized to 1:3, 30 min and 1 h, respectively, for maximum drug loading. The effect of temperature was found to be not significant on maximum amount of drug loading. During preparation of drug resin complex (resinate), the other variables were kept constant. The effect of formulation variables (concentration of ammonium bicarbonate as subliming agent, concentration of crospovidone as superdisintegrant and amount of microcrystalline cellulose (MCC)) and a process variable (compression force) on tablet hardness, disintegration time, and friability was optimized using 24 randomized full factorial design. Accordingly, the various models describing the relationship of the selected variables were obtained using Design-Expert 8.0.7.1 software and the models were analyzed. The corresponding surface response and contour plots were also obtained and the optimum area was determined and, then validated. Simultaneous optimization of the responses gave the most desirable representative optimum formulation, within the common optimum region, with a disintegration time of 17.82 s, ix hardness of 75.49 N and friability 0.40% at ammonium carbonate 14.20%, crospovidone 6.14%, MCC 51.31% and compression force 10.15 KN. The validity of obtained optimal point was confirmed by the low magnitude of percent prediction error. With that a stable, taste-masked MCP ODTs, which is suitable for patients with gastroparesis was developed. The prepared optimized formulations were characterized for powder properties, tablets morphology, in vitro drug release behavior, taste-masking and stability. The study showed that a porous, taste-masked, and stable MCP ODTs with superior in-vitro drug release profile as compared to available marketed products, which is suitable for patients with gastroparesis was developed. Key words: metoclopramide, ion exchange resin, resinate, orally disintegrating tablets, taste-masking, sublimation technique, optimization, full factorial design
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    Formulation and Optimization of Taste-Masked Phenobarbitone Orally Disintegrating Tablets Prepared by Direct Compression Method
    (Addis Ababa University, 2015-05) Gadisa, Wondesen; Belete, Anteneh(PhD); Feleke, Fitsum(PhD)
    Epilepsy is a serious neurological disorder characterized by spontaneous seizures. Despite the development of successive generations of antiepileptic drugs, phenobarbitone has retained a unique position in the therapeutic armamentarium and is still the most widely prescribed drug for treatment of epilepsy throughout the world. However, the pharmaceutical industry supplies oral solid dosage forms that are generally inadequate for pediatric, geriatrics and patients experiencing difficulty in swallowing needs. Therefore, the present study aims at formulation and optimization of taste-masked orally disintegrating tablets of phenobarbitone using direct compression technique for use in specific population such as pediatrics, geriatrics and dysphagia patients. Thus, the study begins with the determination of the bitterness threshold of phenobarbitone in vivo. Then, taste-masked microspheres of phenobarbitone were prepared by oil in water emulsion solvent evaporation technique using Eudragit®E100 as a polymeric material. The effect of formulation variable i.e., polymer: drug ratio at four different levels (1:1, 2:1, 3:1 and 4:1) and process variable, i.e., stirring rate (500, 650 and 800 rpm) were examined. The prepared formulations were characterized for flow properties, particle size distribution, entrapment efficiency and percentage yield. The study revealed that the mean particle size ranged from 386.01 ± 3.88 to 456.72 ± 3.53 μm, the drug encapsulation efficiency varied from 88.50 ± 2.14 to 97.00 ± 1.26% of the theoretical amount incorporated. The taste-masking efficiency was determined by spectrophotometric analysis based on the amount of drug released from tastemasked microspheres in pH 6.8 phosphate buffer after 5 min. Taste evaluation studies confirmed that microspheres of phenobarbitone having a polymer: drug ratio of 1:1 are tasteless. FT-IR spectra of phenobarbitone and the physical mixture of drug and Eudragit®E100 1:1 suggested no interaction between the drug and polymer. x The effect of various formulation and process variable on phenobarbitone orally disintegrating tablets was investigated. The results of the experiments revealed that the major factors that affect the tablet characteristics are compression force, level of superdisintegrant and MCC/mannitol. Besides, since it has significant effect on drug release, the effect of polymer to drug ratio within the microsphere on the various tablet characteristics was also investigated. Thus, four factors, two level (2 4-1) fractional factorial experimental design was selected to investigate the effects of the selected independent variables on the various responses such as disintegration time, wetting time, hardness, drug release in 5 min and drug release in 15 min of taste-masked orally disintegrating tablets (ODTs). Accordingly, the various models describing the relationship of the selected variables were obtained using Design- Expert 8.0.7.1 software and the models were analyzed. The corresponding surface response and contour plots were also obtained and the optimum area was determined and, finally, the optimum was validated. Simultaneous optimization of the responses gave the most desirable representative optimum formulation, within the common optimum region, with a disintegration time of 31.95 sec., wetting time of 46.41 sec., hardness of 52.13 N, drug release within 5 min 62.21%,and drug release within 15 min of 90.03% at compression force 11.29 KN, SSG of 4.6%, MCC/ mannitol ratio of 1.6 :1 and polymer to drug ratio of 1.26:1. The validity of obtained optimal point was confirmed by the low magnitude of percent prediction error. Key words: phenobarbitone, Orally disintegrating tablets, Eudragit®E100, Tastemasking, direct compression, Fractional factorial design
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    Myrrh Resin (Commiphora myrrha) As Rate Controlling Excipient In Sustained Release Matrix Tablets of Theophylline: Evaluation, Formulation and Optimization Study
    (Addis Ababa University, 2014-12) Nigatu, Muluken; Belete, Anteneh(PhD); Mary Joseph, Nisha(PhD)
    Myrrh is an oleo-gum resin, obtained from the stem of various species of Commiphora, Family Burseraceae. The chief source is Commiphora myrrha. Myrrh is phytotoxically safe raw material in industries like pharmaceuticals and food industries. The plant based excipients have been studied for their application in different pharmaceutical dosage forms like matrix sustained release system. Theophylline is used as bronchodilator in the management of asthma and chronic obstructive pulmonary disease. Its narrow therapeutic index (10-20 μg/ml) requires suitable formulation strategies and sustained-release oral formulations have emerged as the most useful approach. The aim of this study was to investigate the myrrh resin from Commiphora myrrha as a rate controlling excipient for sustained release matrix tablets of theophylline. The moisture content and total ash values of myrrh resin was found to be 4.67±0.577% and 0.24±0.047%, respectively. The sustained release matrix tablets of theophylline were prepared by wet granulation technique using myrrh resin as rate controlling excipient. The hardness of different formulations were found to be between 89.8±2.86 and 133.7±3.53N while all tablets have passed the friability test (<1%). Analysis of dissolution data of the formulations indicated that the best fitting is with first order kinetics, whereas the mechanism of drug release pattern follows anomalous or non-fickian diffusion. The myrrh resin amount (A) and compression force (B) were selected as independent variables and drug release at 1 h (rel1 h), 12 h (rel12 h) and time to 50% drug release (t50%) were taken as the response variables. Therefore, the effects of myrrh resin amount (A) and compression force (B) were further studied and optimized for the desired outputs using central composite design statistical approach. Design-Expert 8.0.7.1 software was employed to carry out the experimental design, statistical analysis, numerical and graphical optimization. By comparing several statistical parameters, linear model was selected for both rel1 h and rel12 h whereas quadratic model was found to be the best fit model for t50%. The adequacy of the models was checked by analysis of variance (ANOVA). The ANOVA results revealed that both models II have significant values indicating the terms in the models have significant effect (P < 0.05) on the responses except the interaction effect (AB) of quadratic model which was found to be insignificant. Model simplification was carried out by eliminating this term (AB) in polynomial equations in order to improve the model. Optimization was achieved by simultaneous optimization of rel1 h, rel12 h and t50%. An optimum region of 24.981%, 91.217% and 2.861 h was obtained by the software for rel1 h, rel12 h and t50% , respectively when 17.5% myrrh resin amount (MRA) and 13.9 KN compression force (CF) was used. The kinetic study showed the optimized formulation followed first order kinetics model with anomalous release mechanism. In validation of the optimized formulation, the experimental values were found to be in close agreement with the predicted values confirming the predictability and validity of the model. This demonstrated that the optimization technique was successful in designing the theophylline sustained release matrix tablet formulation by using myrrh resin as rate controlling excipient. The Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed the absence of incompatibility between theophylline and the myrrh resin. Therefore, the myrrh resin can be used as a potential alternative rate controlling excipient for sustained release formulation. Keywords: Myrrh resin, theophylline, sustained release, matrix tablet, optimization, central composite design
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    Preparation and Evaluation of Dual Modified Ethiopian Yam (Dioscorea abyssinica) Starch for Sustained Release Tablet Formulation
    (Addis Ababa University, 2013-01) Mulualem, Yohaness; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    Starch has been the subject of intensive research over many decades due to the fact that native starches are diverse, biodegradable, applications are enormous and modifications to starch are numerous. In this study, Dioscorea abyssinica (boyna) starch has been chemically modified with the aim of determining its potential for sustained release application. It was chemically modified by cross-linking using sodium hexametaphosphate (SHMP), acetylating with acetic anhydride and dual modified - cross-linking followed by acetylation. Cross-linked starches (CLSs) with degree of cross-linking (DC) of 54.46, 62.20 and 68.88 (%), CLS-A, CLS-B, CLS-C respectively, were obtained while cross-linking the native starch (NS) with 5, 10, and 15% SHMP for 6 h. By reacting boyna starch with acetic anhydride (AA) in ratios of 1:1 and 1:2, starch acetates (SAs) with degrees of substitution of 0.339 (SA-A) and 0.546 (SA-B), were obtained, respectively. In an attempt to prepare a dual modified starch (DMS), the CLSs were acetylated in a similar condition as the NS. The physicochemical, material, and tablet forming properties of the modified starches were investigated to determine potential usages in sustained release applications. In moisture sorption study, CLSs exhibited the lowest water-uptake and SAs notably increased the sorption capacity of the NS and CLS. Cross-linking decreased the swelling power of the NS as the level of SHMP was increased while acetylation showed the opposite effect. The reduction observed in viscosity values indicated the effectiveness of cross-linking in reducing swelling of the NS. On the basis of powder properties analyses, it was evident that acetylation improved the poor flow properties of CLSs and NS. SAs were found to be free flowing with angles of repose of 25.11O and 23.02O and flow rate of 3.09 and 10.54 g/sec, respectively for SA-A and SA-B. The Hausner ratio of the SAs was 1.18 and 1.25 and Carr’s index of 22.36 and 20.24, respectively for SA-A and SA-B. Tablets were prepared and evaluated for hardness, tensile strength, friability, and disintegration time. Results indicated that both cross-linking and acetylation processes improved tablet forming properties of the NS with more significant effect in the dual modified starches. The Fourier transform infrared (FTIR) spectra revealed that a structural change occurred in the NS because of cross-linking and acetylation. Correspondingly, the spectral analysis proved that the dual modified starches are compatible with theophylline. iv Dissolution studies of theophylline loaded modified starches were performed for 12 h. Matrix tablets containing Ac-CLS-F, where CLS-C reacted in a 1:2 ratio with AA, loaded with 20, 30 and 40% theophylline and Ac-CLS-E, where CLS-C reacted in a 1:1 ratio with AA, loaded with 20% theophylline were studied for drug release. And 80% of theophylline was released in about 10.62, 9.35, and 8.18 h from 20, 30 and 40% theophylline loaded Ac-CLS-F, respectively, whereas 20% theophylline loaded Ac-CLS-E released its drug content within about 12 h of the dissolution study. The dissolution data was subjected to the various drug release kinetic models and the data best fitted Higuchi model with R2 > 0.994. The drug release diffusional exponent (n), with goodness of fit > 0.988 obtained for Korsemeyer-Peppas model for 20, 30 and 40% drug loaded Ac-CLS-F varied between 0.452-0.530 indicating deviation from Fickian diffusion mechanism whereas a quasi-Fickian diffusion behavior was exhibited (n = 0.31) for 20% loaded Ac-CLS-E. From the foregoing, it can be concluded that Ac-CLS-F could have a potential for use as a sustained release excipient. Key words: Dioscorea abyssinica, Boyna starch, Cross-linking, Acetylation, Dual modification, Sustained release.
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    Preparation, characterization and Optimization of oromucosal Clotrimazole Emulgel formulation
    (Addis Ababa University, 2015-03) Mengesha, Mahilet; Gebre-Mariam, Tsige (Professor); Belete, Anteneh(PhD)
    The topical applications of a drug to the oral mucosa offer the potential advantages of delivering the drug directly to the site of action and possibly delivering the drug for an extended period of time. The environment of the oral cavity and the continual secretion and swallowing of saliva are unique problems which need to be considered to ensure successful delivery of a drug via this route. Recently, emulgel has emerged as one of the most interesting topical preparations in the field of pharmaceutics. The use of emulgel as a delivery system has several advantages such as ease of administration, increased residence time of the drug at the applied site, and better drug release and diffusion. The objectives of this study were to formulate Clotrimazole, a practically insoluble imidazole antifungal, as oromucosal emulgel formulation, characterize, optimize, and to study the release profile and storage stability of the formulation. Different oils were compared for their solubilizing capacity of clotrimazole and phase diagrams were constructed using Tween 80 and ethanol as an emulsifier and co-emulsifier, respectively. Two of the commonly used polymers, sodium carboxymethyl cellulose (Na CMC) and hydroxypropylmethyl cellulose (HPMC), were studied for their gelling capacity. A systematic experimental design and optimization approach was carried out using central composite design (CCD) to select study points and generate polynomial equations which describe the relationship between the dependant and independent variables. The formulated emulgels were characterized by their physical behavior, content, pH, apparent viscosity, in vitro release, relative in vitro residence time, and spreadability using modified and standard methods. The mean globule size, release profiles, mechanisms, and kinetics of the optimized formulations were compared and studied. Based on relative solubility study oleic acid and virgin olive oil were chosen as oil phase and it was found that Tween 80 and ethanol at a ratio of 2:1 managed to emulsify the oil phase with greater area of transparent emulsions in the phase diagram. The emulsions were jellified using Na CMC without disrupting their phase behavior. Rheological studies revealed that the clotrimazole emulgels exhibited a shear-thinning behavior which is desirable for ease of administration. Based on the predicted responses and their desirability indices, three xiii formulations were selected as the optimum formulations with oil phase concentration of around 12.4%, surfactant solution concentration of 30%, and Na CMC concentration of 4%. The optimized clotrimazole emulsions exhibited 139-146 nm and 0.16-0.26 of mean globule size and polydispersity, respectively. When in-vitro drug release data were fitted to five commonly employed release kinetic models, zero order release model showed the best fit with high linearity for all the optimized formulations. The polymer relaxation and erosion were found to be the rate controlling steps when the first 60% drug releases were fitted to the Korsmeyer-Peppas model. From this, it can be concluded that clotrimazole can be formulated as an emulgel which can possibly enhance its release in aqueous media with acceptable spreadability and residence time at the target site. Keywords: Emulgel; Clotrimazole; Oral candidiasis; Optimization; Shear thinning.
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    solation, Evaluation and Optimization of Waste Derived Citrus Aurantifolia Peel Pectin as a Polymer in Furosemide Floating and Bioadhesive Matrix Tablet Formulation
    (Addis Ababa University, 2023) Abdela,Ebrahim; Belete, Anteneh(PhD); Mulualem,Yohannes
    The Citrus aurantifolia (Christm) Swingle species can be found in many parts of the world including the subtropical and tropical areas. It is a small shrubby tree, about 5 m length and has fruit has globule to oval nearly 3-6 cm diameter with a color range from light yellow to purple. Some studies revealed that citrus waste derived pectin- becoming promising way for based gastro- retentive (floating and bioadhesive) drug delivery systems formulation due to pectin’s economic, environmental and health related benefits. However, the floating and bioadhesive ability of the citrus aurantifolia peel pectin is not yet established. The bioavailability of furosemide is irregular through oral route and subjected to inter- or intra-subject variability. Hence, on the basis of its physico- chemical properties, it is a candidate drug for gastro-retentive formulations. Therefore, this study aimed to evaluate the potential of citrus Aurantifolia peel pectin as a polymer for preparing floating and bioadhesive matrix tablet using furosemide as a model drug. The citrus peel pectin was extracted from local citrus aurantifolia tree fruit peel using hot water extraction technique and characterized for several physicochemical properties such as the presence of carbohydrate, loss on drying, total ash, pH, water solubility index, swelling power, relative solubility, moisture sorption-desorption pattern, viscosity, powder flow properties and its compatibility with the model drug were investigated. Wet granulation method was employed to prepare the furosemide granules and the prepared granules were evaluated for particle size and distribution, bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate, and the friability of the formulated tablets were evaluated. Other tablet quality parameters including friability, hardness, thickness, diameter, weight variation and content uniformity were assessed and in acceptable pharmacopeial standard. Based on the preliminary investigation, the pectin (10-40%) and effervescent agent (NaHCO3) (5-20%) concentrations were significantly affecting the response variables (p value < 0.05) such as floating duration (FD), bioadhesive strength (BS), swelling index (SI), drug release at 1 hr (DR1hr) and drug release rate (DRR)). Hence, further optimization study was conducted using central composite design (CCD) approach of design-expert 13 software. Both numerical and graphical optimization techniques were used for optimization. The Citrus aurantifolia tree fruit peel yielded 34.4% (w/w) purified pectin with light yellow color. Its pH and ash values were 4.6 and 2.29%, respectively. It showed solubility in hot water. The equivalent weight, methoxy content, anhydronic acid, and the degree v of esterification were 81.5, 13.84, 91.68, and 85.49, respectively which showed high methoxy pectin. The purified pectin powder had a Carr’s index of 36.6, Hausner ratio of 1.36 and angle of repose 32.78o which necessitates to conduct wet granulation technique. The compatibility study using FTIR and DSC analysis revealed that furosemide and citrus peel pectin were compatible. The drug release kinetic analysis of 13 formulations as per the CCD revealed best fits for Higuchi model with diffusion and erosion release mechanisms. The optimization results indicated that quadratic model was selected for swelling index and linear for the other responses. The adequacy of the model was evaluated using analysis of variance (ANOVA). Accordingly, the model provided an optimum formulation at 22.3% of pectin concentration and 5 % of effervescent agent. Under this condition, the software predicted floating duration (14.07 %), bioadhesive strength (28.57gm), swelling index (254.08%), drug release at 1hr (27.86%) and drug release rate (28.045 % / h-1/2). The optimization result predicted the optimized value of the independent variables to achieve desired responses was evaluated. The validity of this optimum formulation was confirmed experimentally. Based on the experimental studies, the validity of the model or software prediction was confirmed and the relative error are less than 5%. The flowability of the granule of optimized tablet was found excellent as the angle of repose was found to be <300 while the Carr’s and Hausner ratios were determined as < 10 and < 1.11 respectively. In conclusion, the results of this study enable to suggest that waste-derived citrus pectin can be used as an abundant alternative pharmaceutical excipient in the formulation and manufacture of floating and bioadhesive matrix tablets, leading to the formulation of an optimal floating and bioadhesive formulation