RÉSUMÉ
Artemether-lumefantrine (AL) is a highly effective and commonly used Artemisinin-based Combination Therapy (ACT) for treating uncomplicated malaria caused by Plasmodium falciparum, including drug-resistant strains. However, ineffective regulatory systems in resource-limited settings can lead to the infiltration of poor-quality and counterfeit antimalarial medicines into the pharmaceutical supply chain, causing treatment failures, prolonged illness, and disease progression. The objective of the study was to assess the quality of selected brands of fixed-dose combination (FDC) AL tablets and suspensions marketed in Kumasi, Ghana. A total of fourteen brands of FDC AL medicines, comprising eight tablets and six suspensions were purchased from various retail pharmacy outlets in Kumasi, Ghana. All samples were subjected to thorough visual inspection as a quick means of checking quality through meticulous observation of the packaging or dosage form. The quality parameters of the tablets were determined using uniformity of weight, hardness, friability, and disintegration tests. Suspensions were assessed based on pH and compared with the British Pharmacopeia (BP) standard. The samples were then analyzed for drug content (assay) using reverse-phase high-performance liquid chromatography (RP-HPLC). All the tablet samples conformed to BP specification limits for uniformity of weight (deviation of less than ± 5%), hardness (4.0-10 kg/mm2), friability (<1%), and disintegration time (<15 minutes). The active pharmaceutical ingredients' quantitative assay demonstrated that all the tablets met the BP specifications (90-110%). The results of the pH studies showed that out of the six brands of suspension investigated, five (83.3%) were compliant with the official specification for pH, while one (16.7%) failed the requirement. Unlike the tablet brands, drug content analysis of the six suspensions showed that two (33.3%) were substandard. The artemether and lumefantrine contents in these failed suspensions were variable (artemether: 81.31%-116.76%; lumefantrine: 80.35%-99.71%). The study results indicate that most of the tested products met the required quality standards, demonstrating satisfactory drug content and other quality specifications. The presence of substandard drugs underscores the necessity for robust pharmacovigilance and surveillance systems to eliminate counterfeit and substandard drugs from the Ghanaian market.
RÉSUMÉ
Developing countries face enormous challenges with substandard and falsified antimalarial drugs. One specific issue is the lack of a simple, cost-effective, and robust HPLC method to simultaneously determine and quantify the active pharmaceutical ingredients (APIs) in fixed-dose artemether-lumefantrine pharmaceutical dosage forms. The current study developed a novel, simple, sensitive, precise, accurate, and cost-effective RP-HPLC method for the simultaneous determination and quantification of artemether and lumefantrine in pharmaceutical dosage forms. The HPLC analysis was carried out on an Agilent 1260 Infinity Series HPLC system equipped with an ODS Intersil-C8 (150 × 4.6 mm) 5.0 µm column, by isocratic elution. The mobile phase composition consisted of acetonitrile and 0.05% orthophosphoric acid buffer of pH 3.5 in the ratio of 70 : 30 v/v. The analysis was performed at a 1 mL/min flow rate and a column temperature of 25°C. The total run time was 6 minutes. The detection was done with a variable wavelength detector (VWD) at an isosbestic point wavelength (λ) of 210 nm. The developed method was validated according to the ICH guidelines concerning system suitability, specificity, linearity, accuracy, precision, and robustness. The system suitability of the developed method revealed satisfactory theoretical plates and symmetry factors. The method proved to be specific, with no interference of mobile phase or excipients. The calibration plot exhibited linearity over the concentration range of 275-1925 µg/mL with R2 = 0.9992 for artemether and a range of 150-1050 µg/mL with R2 = 0.9985 for lumefantrine. The accuracy of the method, determined by the recovery study, was 99.79-100.16% for artemether and 99.04-99.50% for lumefantrine. The % RSD values for intraday precision were 0.175 and 0.203, while interday precision values were 0.340 and 0.554 for artemether and lumefantrine, respectively. The method demonstrated robustness when subjected to slight modifications in the flow rate, column temperature, and mobile phase composition. The developed analytical method proved satisfactory as per ICH guidelines and hence can be used for the determination and quantification of artemether and lumefantrine in bulk drug and pharmaceutical dosage forms.
RÉSUMÉ
Acne vulgaris is an inflammatory skin condition that affects virtually everyone at some point. Papules, comedones, pustules, scarring, and nodules are standard features of the disease and can have a detrimental social and psychological impact on an individual. Although allopathic acne treatments are available, they have adverse side effects, are expensive, and are prone to cause antibiotic resistance. The present study is aimed at formulating and evaluating topical gels containing Aloe vera, Allium cepa, and Eucalyptus globulus extracts as potential antiacne drugs. Six formulations containing the herbal extracts were prepared using 1% Carbopol 940 as a gelling agent. The phytochemical composition of the plant extracts was determined. The extracts and gels' minimum inhibitory concentration (MIC) was assessed using the microbroth dilution method. The physicochemical properties of the formulated gels, such as homogeneity, colour, texture, odour, grittiness, spreadability, extrudability, viscosity, pH, and drug content, were evaluated. All the plant extracts contained alkaloids, flavonoids, tannins, triterpenoids, and coumarins. The gel formulations showed varying activity against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa at various concentrations. The phytochemical components of the plant extracts are probably responsible for the antimicrobial activity of the gel formulations. The 5% Aloe vera-Allium cepa (1 : 1) combination gel formulation showed excellent activity against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans, with MICs of 12.50, 25.00, 6.25, 25.00, and 12.50 mg/mL, respectively. The gels generally had good physicochemical and antimicrobial properties and could be used as antiacne remedies.
Sujet(s)
Acné juvénile , Anti-infectieux , Humains , Anti-infectieux/pharmacologie , Anti-infectieux/usage thérapeutique , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Acné juvénile/traitement médicamenteux , Composés phytochimiques/pharmacologie , Tests de sensibilité microbienne , Candida albicans , Gels/pharmacologie , Escherichia coliRÉSUMÉ
The development of a raw material into an acceptable pharmaceutical excipient involves evaluation of the physicochemical and formulation properties of the potential raw material. Results from these evaluations may serve as a guide to subsequent use of the substance. The objective of the study was to evaluate the physicochemical and microbiological properties of the stem bark gum of Cordia millenii tree in conventional release paracetamol tablets. From the physicochemical evaluations, the gum was slightly acidic and soluble in all the aqueous-based solvents, except 0.1 N HCl in which it was sparingly soluble. All the absorptive properties of the gum indicated tablet disintegrating potential for tablet formulation. The total ash of the gum was higher than that of the international standard gum arabic. Micromeritic properties of the gum indicated the need for a flow aid to improve its flowability. There were no harmful microorganisms detected in the gum. Aerobic organisms and moulds and yeast were detected within permissible limits. Tablets formulated using six different concentrations of gum dispersions as a binder were generally soft and failed the USP T80 standard of dissolution, indicating poor binding and drug releasing properties. Quality control properties of three different batches of tablets containing varying concentrations of the dry gum as a disintegrating agent were comparable to tablets containing equal concentrations of corn starch. The in vitro drug releases were similar at all-time points of drug evaluation. The gum can therefore be considered as a good disintegrant in the formulation of conventional release tablets.
Sujet(s)
Cordia , Cordia/composition chimique , Arbres , Écorce , Excipients/composition chimique , Comprimés/composition chimique , SolubilitéRÉSUMÉ
Pharmaceutical oral solutions are preparations in which the active ingredients are dissolved in suitable liquid vehicles such as syrups. This study sought to determine the potential of glucose syrup produced from high quality cassava flour (HQCF) as a vehicle or sweetener in the preparation of paracetamol syrup and simple linctus. Four formulations (two paracetamol syrups (B1 and B2) and two simple linctus formulations (A1 and A2)) were prepared using glucose syrup from HQCF as vehicle or sweetener while two controls (B3 and A3) were prepared for each group using sucrose syrup as vehicle or sweetener. Two brands of paracetamol syrup and simple linctus were purchased from retail pharmacies to serve as standards. Physical and organoleptic parameters such as pH, taste and color, microbial load, and drug content of all formulations were determined. All formulations passed the microbial load and drug content tests as specified by the British Pharmacopoeia. The paracetamol syrups were all sweet with characteristic bitter aftertastes except formulation B2 which was sweetened with sucralose. All the simple linctus formulations were sweet except A2 (sweetened with sucralose) which was very sweet. The taste masking capacity of the glucose syrup produced from HQCF matched that of the sucrose syrup in the products formulated. Therefore, glucose syrup from HQCF could be a suitable alternative to sucrose syrup as a vehicle or sweetener in oral liquid formulations and can ultimately reduce the cost of these oral liquid formulations.
RÉSUMÉ
Polymeric materials from plants continue to be of interest to pharmaceutical scientists as potential binders in immediate release tablets due to availability, sustainability, and constant supply to feed local pharmaceutical industries. Paracetamol tablet formulations were utilized in investigating the potential binding characteristics of pectin harnessed from various okra genotypes (PC1-PC5) in Ghana. The pectin yields from the different genotypes ranged from 6.12 to 18.84%w/w. The pH of extracted pectin ranged from 6.39 to 6.92, and it had good swelling indices and a low moisture content. Pectin extracted from all genotypes were evaluated as binders (10, 15, and 20%w/v) and compared to tragacanth BP. All formulated tablets (F1-F18) passed the weight uniformity, drug content, hardness, and friability tests. Based on their crushing strength, tablets prepared with pectin from the various genotypes were relatively harder (P ≤ 0.05) than tablets prepared with tragacanth BP. Tablets prepared with pectins as binders at 10%w/v and 15%w/v passed the disintegration and dissolution tests with the exception of PC4 at 15%w/v. Incorporation of pectin from all genotypes (excluding PC5) as a binder at concentrations above 15%w/v (F13, F16, F14, and F15) produced tablets which failed the disintegration test and showed poor dissolution profiles. Thus, pectin from these genotypes can be industrially commodified as binders in immediate release tablets using varying concentrations.
Sujet(s)
Abelmoschus/composition chimique , Pectine/composition chimique , Comprimés/composition chimique , Acétaminophène/composition chimique , Chimie pharmaceutique/méthodes , Excipients/composition chimique , Génotype , Ghana , Solubilité/effets des médicaments et des substances chimiquesRÉSUMÉ
Okra pectin has been studied as a potential excipient in tablet formulations for pharmaceutical industries. Okra is widely grown and available in Ghana and other parts of the world. The prospective use of pectin from okra genotypes grown in Ghana as tablet disintegrants has not been reported. This study aims to determine the potential and comparative disintegrating properties of pectin from five okra genotypes (Abelmoschus esculentus L.) in Ghana using uncoated immediate release paracetamol tablet formulations. The yield of the pectin from the various genotypes ranged between 6.12 and 18.84% w/w. The extracted pectins had pH ranging from slightly acidic to almost neutral (6.39-6.92). Pectin from the various genotypes exhibited good swelling indexes (Ë200%), varying solubility in different solvents, and low moisture content (Ë20%). Elemental analysis of the extracted pectin from the various genotypes revealed very low levels of toxic metals and micronutrients. Pectin from the various genotypes was evaluated as disintegrants within concentrations of 5-10% w/w (F1-F18). Their disintegrating properties were compared to that of maize starch BP. All the formulated batches of uncoated immediate release paracetamol tablets (F1-F18) passed the following: uniformity of weight test, uniformity of dimensions, hardness, friability (Ë1%), and drug content (95-105%). Significant differences (p ≤ 0.05) were observed between the hardness of the maize starch tablets and tablets formulated from pectin of the various genotypes. Pectin from all genotypes other than PC5 exhibited good disintegrating properties (D T Ë 15 min) and subsequently passed the dissolution profile test (≥70% release in 45 minutes). Tablets formulated with PC5 as disintegrants at all concentrations (5% w/w (F5), 7.5% w/w (F11), and 10% w/w (F17)) failed the disintegration and dissolution tests. Ultimately, pectins extracted from PC1, PC2, PC3, and PC4 can be commercially exploited as disintegrants in immediate release tablets.
RÉSUMÉ
The potential of cocoa pod husk (CPH) pectin-based modified release (MR) capsules as a carrier for chronodelivery of hydrocortisone in Sprague-Dawley rats was assessed. Extemporaneously formulated CPH pectin-based hydrocortisone (10 mg) capsules crosslinked with calcium chloride (Formulation A) or zinc (Formulation B) and a commercial immediate release hydrocortisone formulation were administered orally to Sprague-Dawley rats and the pharmacokinetic parameters were evaluated using noncompartmental analysis. Formulation A had a 2 h lag phase followed by an increase in serum drug concentration in the treated rats. Peak concentrations (Cmax) of 21.799 ± 1.993 ng/ml and 20.844 ± 2.661 ng/ml were achieved after 6 ± 0.23 h and 6 ± 0.35 h (Tmax), respectively, for capsules A and B. The immediate release formulation had a peak concentration of 15.322 ± 0.313 ng/ml within 1 ± 0.2 h. The relative bioavailability of the CPH pectin-based capsules A and B was 213% and 274%, respectively. Formulations A and B had half-lives more than three times that of the immediate release formulation. The MR capsules exhibited a higher exposure, greater bioavailability, and versatility in release of cortisol than the commercial immediate release formulation. Additionally, the MR capsules exhibited an extended drug release with overnight cortisol rise and early morning cortisol peak and hold promise in the management of adrenal insufficiency.
RÉSUMÉ
The quality of 68 samples of 15 different essential children's medicines sold in licensed medicine outlets in the Ashanti Region, Ghana, was evaluated. Thirty-two (47.1%) of the medicines were imported, mainly from India (65.6%) and the United Kingdom (28.1%), while 36 (52.9%) were locally manufactured. The quality of the medicines was assessed using content of active pharmaceutical ingredient (API), pH, and microbial limit tests, and the results were compared with pharmacopoeial standards. Twenty-six (38.2%) of the samples studied passed the official content of API test while 42 (61.8%) failed. Forty-nine (72.1%) of the samples were compliant with official specifications for pH while 19 (27.9%) were noncompliant. Sixty-six (97.1%) samples passed the microbial load and content test while 2 (2.9%) failed. Eighteen (26.5%) samples passed all the three quality evaluation tests, while one (1.5%) sample (CFX1) failed all the tests. All the amoxicillin suspensions tested passed the three evaluation tests. All the ciprofloxacin, cotrimoxazole, flucloxacillin, artemether-lumefantrine, multivitamin, and folic acid samples failed the content of API test and are substandard. The overall API failure rate for imported products (59.4%) was comparable to locally manufactured (63.9%) samples. The results highlight the poor quality of the children's medicines studied and underscore the need for regular pharmacovigilance and surveillance systems to fight this menace.
RÉSUMÉ
Natural polymer research has recently become the focus of intensive research in the quest for new enabling excipients for novel drugs in pharmaceutical formulation for optimal treatment outcomes. Evaluations of some excipients have shown deleterious haematological effects of varying extents on the safety profile of these excipients. A 90-day subchronic toxicity study was conducted to evaluate the influence of cocoa pod husk (CPH) pectin on indicators for haematotoxicity. Male and female Sprague Dawley rats (SDRs) were fed with CPH pectin in doses up to 71.4 mg/kg. The effects of CPH pectin on the haematological indices, direct and total bilirubin, and the spleen were determined. The results indicated that CPH pectin did not induce any untoward toxic effects on the haematological indices, bilirubin levels, and the spleen. There were, however, elevations in MCV at day 30, which was not sustained after the 90 days. The data obtained from this study did not reveal any remarkable findings of toxicological relevance to the haematopoietic system.
RÉSUMÉ
The disintegrant potential of native starches of five new cassava (Manihot esculenta Crantz.) varieties developed by the Crops Research Institute of Ghana (CRIG) was studied in paracetamol tablet formulations. The yield of the starches ranged from 8.0 to 26.7%. The starches were basic (pH: 8.1-9.9), with satisfactory moisture content (≤15%), swelling capacity (≥20%), ash values (<1%), flow properties, and negligible toxic metal ion content, and compatible with the drug. The tensile strength (Ts ), crushing strength (Cs ), and friability (Ft ) of tablets containing 5-10% w/w of the cassava starches were similar (p > 0.05) to those containing maize starch BP. The disintegration times of the tablets decreased with increase in concentration of the cassava starches. The tablets passed the disintegration test (DT ≤ 15 min) and exhibited faster disintegration times (p > 0.05) than those containing maize starch BP. The disintegration efficiency ratio (DER) and the disintegration parameter DER c of the tablets showed that cassava starches V20, V40, and V50 had better disintegrant activity than maize starch BP. The tablets passed the dissolution test for immediate release tablets (≥70% release in 45 min) with dissolution rates similar to those containing maize starch BP.
RÉSUMÉ
An isocratic sensitive and precise reverse phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination and quantification of hydrocortisone in controlled-release and conventional (tablets and injections) pharmaceutical preparations. Chromatographic separation was achieved on an ODS (C18), 5 µm, 4.6 × 150 mm, with an isocratic elution using a freshly prepared mobile phase of composition methanol : water : acetic acid (60 : 30 : 10, v/v/v) at a flow rate of 1.0 ml/min. The detection of the drug was successfully achieved at a wavelength of 254 nm. The retention time obtained for the drug was 2.26 min. The proposed method produced linear detectable responses in the concentration range of 0.02 to 0.4 mg/ml of hydrocortisone. High recoveries of 98-101% were attained at concentration levels of 80%, 100%, and 120%. The intraday and interday precision (RSD) were 0.19-0.55% and 0.33-0.71%, respectively. A comparison of hydrocortisone analyses data from the developed method and the official USP method showed no significant difference (p > 0.05) at a 95% confidence interval. The method was successfully applied to the determination and quantification of hydrocortisone in six controlled-release and fifteen conventional release pharmaceutical preparations.
RÉSUMÉ
This study evaluated the in vitro potential of cocoa pod husk (CPH) pectin as a carrier for chronodelivery of hydrocortisone intended for adrenal insufficiency. FTIR studies found no drug-CPH pectin interactions, and chemometric analysis showed that pure hydrocortisone bears closer similarity to hydrocortisone in hot water soluble pectin (HWSP) than hydrocortisone in citric acid soluble pectin (CASP). CPH pectin-based hydrocortisone matrix tablets (~300 mg) were prepared by direct compression and wet granulation techniques, and the tablet cores were film-coated with a 15% HPMC formulation for timed release, followed by a 12.5% Eudragit® S100 formulation for acid resistance. In vitro drug release studies of the uncoated and coated matrix tablets in simulated gastrointestinal conditions showed that wet granulation tablets exhibit greater retardation of drug release in aqueous medium than directly compressed tablets. CASP showed greater suppression of drug release in aqueous medium than HWSP. Wet granulation HWSP-based matrix tablets coated to a final coat weight gain of ~25% w/w were optimized for chronodelivery of hydrocortisone in the colon. The optimized tablets exhibited a lag phase of ~6 h followed by accelerated drug release in the colonic region and have potential to control night time cortisol levels in patients with adrenal insufficiency.
RÉSUMÉ
Oral dissolvable films (ODFs) of diclofenac sodium intended for osteoarthritis were prepared using Albizia and Khaya gums as hydrophilic film formers. The physicochemical properties of the gums were characterized and the gums were used to prepare diclofenac sodium ODFs (~50 mg/4 cm(2) film) by solvent casting. The two gums showed satisfactory film forming properties. The physicomechanical properties, drug-excipient compatibility, and in vitro drug release of the films in phosphate buffer pH 6.8 were studied. Khaya gum had higher extraction yield, moisture content, insoluble matter and true density while Albizia gum showed greater swelling capacity, solubility, and minerals content. The ODFs were thin, soft, and flexible with smooth glossy surfaces and possessed satisfactory physicomechanical properties. FTIR studies showed that no interaction occurred between the drug and the gums. The ODFs disintegrated in <45 s achieved >75% drug release within 7 min with dissolution efficiencies of ~83-96%. Drug releases from F2, F3, F4, F5, and F6 were similar to F1 (p > 0.05; f1 < 15 and f2 ≥ 50) while F7 differed markedly from F1 (p < 0.001; f1 > 15 and f2 < 50). Drug release followed the Higuchi kinetic model which is indicative of Fickian drug diffusion.
RÉSUMÉ
The physicochemical and antimicrobial properties of cocoa pod husk (CPH) pectin intended as a versatile pharmaceutical excipient and nutraceutical were studied. Properties investigated include pH, moisture content, ash values, swelling index, viscosity, degree of esterification (DE), flow properties, SEM, FTIR, NMR, and elemental content. Antimicrobial screening and determination of MICs against test microorganisms were undertaken using agar diffusion and broth dilution methods, respectively. CPH pectin had a DE of 26.8% and exhibited good physicochemical properties. Pectin had good microbiological quality and exhibited pseudoplastic, shear thinning behaviour, and high swelling capacity in aqueous media. The DE, FTIR, and NMR results were similar to those of previous studies and supported highly acetylated low methoxy pectin. CPH pectin was found to be a rich source of minerals and has potential as a nutraceutical. Pectin showed dose-dependent moderate activity against gram positive and gram negative microorganisms but weak activity against Listeria spp. and A. niger. The MICs of pectin ranged from 0.5 to 4.0 mg/mL, with the highest activity against E. coli and S. aureus (MIC: 0.5-1.0 mg/mL) and the lowest activity against A. niger (MIC: 2.0-4.0 mg/mL). The study has demonstrated that CPH pectin possesses the requisite properties for use as a nutraceutical and functional pharmaceutical excipient.
RÉSUMÉ
The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (â¼100 mg) and metformin hydrochloride (â¼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (â¼24 h) and metformin (â¼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.
RÉSUMÉ
This study evaluated the wound healing potential of Spathodea campanulata stem bark in Sprague Dawley rats using the excision wound model. The methanol extract contained glycosides, flavonoids and tannins, and was relatively stable when stored at the room temperature for six (6) months. Solvent-free, semi-solid extract of S. campanulata was incorporated into an aqueous cream and applied (10 % w/w and 20 % w/w) on excision wounds of thirty two (32) rats. Cicatrin(®) cream was used as a standard wound healing agent. Prior to the remedial cream application, done later on twice daily, sixteen (16) rats had their wounds infected with Staphylococcus aureus, while in the remaining sixteen the wounds were kept clean. The surface area of the excision wounds was monitored planimetrically every four (4) days until a complete wound closure or healing took place. Excision wounds treated with 20 % w/w Spathodea cream and Cicatrin(®) cream showed a rapid and comparable decrease (p > 0.05) in wound size. In uninfected wounds, both 20 % w/w Spathodea cream and Cicatrin(®) cream application resulted in â¼ 95 %-wound closure seen on Day 20, and a complete closure seen on Day 24. In infected wounds, both 20 % w/w Spathodea cream and Cicatrin(®) cream administration led to â¼ 91 %-wound closure on Day 24 and a complete wound contraction on Day 28. The results of this study justify the folkloric use of S. campanulata stem bark to the effect of wound treatment.
Sujet(s)
Bignoniaceae/composition chimique , Écorce/composition chimique , Extraits de plantes/pharmacologie , Staphylococcus aureus/effets des médicaments et des substances chimiques , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Infection de plaie/traitement médicamenteux , Plaies et blessures/traitement médicamenteux , Administration par voie topique , Animaux , Antibactériens/usage thérapeutique , Modèles animaux de maladie humaine , Émollient/pharmacologie , Mâle , Méthanol , Répartition aléatoire , Rats , Rat Sprague-Dawley , Infections à staphylocoques/traitement médicamenteux , Résultat thérapeutique , Infection de plaie/microbiologieRÉSUMÉ
The gastrointestinal transit and in vivo drug release behaviour of a film-coated tablet formulation was investigated in five healthy human subjects using the technique of gamma scintigraphy. The film coating system consisted of a mixture of pectin, chitosan and HPMC in a ratio of 6:1:0.37 applied to 750 mg cores at a coat weight gain of 9%. The estimated mean values of the gastric emptying time (62+/-17 min), small intestinal transit time (219+/-53 min), ileocaecal junction lag time (79+/-30 min) and the colon arrival time (345+/-33 min), were similar to published values for the transit of similar sized tablets in humans. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach and the small intestine. There was increased release of radioactivity when the tablets were in the colon due to increased degradation of the film coatings by pectinolytic enzymes resident in the colon. The pectin/chitosan/HPMC film coating system thus acts as a colonic delivery system.
Sujet(s)
Chitine/analogues et dérivés , Côlon/métabolisme , Lactose/analogues et dérivés , Méthylcellulose/analogues et dérivés , Comprimés entérosolubles/pharmacocinétique , Acétaminophène/composition chimique , Administration par voie orale , Adulte , Chitine/composition chimique , Chitosane , Côlon/imagerie diagnostique , Préparations à action retardée , Stabilité de médicament , Vidange gastrique , Transit gastrointestinal , Humains , Lactose/composition chimique , Mâle , Méthylcellulose/composition chimique , Oxazines , Pectine/composition chimique , Scintigraphie , Comprimés entérosolubles/composition chimique , Facteurs tempsRÉSUMÉ
A study was carried out into the biphasic drug release properties of film-coated paracetamol tablets. The tablet cores were formulated without a disintegrant and film-coated with a coating formulation consisting of pectin, chitosan and hydroxypropylmethylcellulose in a ratio of 6:1:0.37. The tablet cores and the film-coated tablets with coat weight gains (CWGs) of 6, 9 and 13% were evaluated for their water absorption (swelling) and drug release properties. All the tablets absorbed water from pH 6.0 Sorensen's phosphate buffer and the amount of water absorbed increased with an increase in tablet CWG. The addition of 100 microl/50 ml pectinolytic enzymes to the medium resulted in at least a 40% reduction in the amount of water absorption by the tablets, as compared to the medium without enzymes. When the enzyme concentration was increased to 200 microl/50 ml, there was a further reduction ( approximately 8% w/w) in the amount of water absorbed by the tablets. Drug release was controlled in upper gastrointestinal fluids and decreased with an increase in tablet CWG. Drug release was, however, accelerated in the presence of pectinolytic enzymes, consistent with the entry of the tablets in the colon. An evaluation of the drug release data by the Korsmeyer-Peppas equation showed the involvement of molecular diffusion and other factors such as film/tablet erosion and drug dissolution in drug release.
Sujet(s)
Préparations pharmaceutiques/métabolisme , Comprimés entérosolubles/pharmacocinétique , Acétaminophène/composition chimique , Acétaminophène/pharmacocinétique , Chimie pharmaceutique , Préparations pharmaceutiques/composition chimique , Comprimés entérosolubles/composition chimiqueRÉSUMÉ
Mixed films containing pectin, chitosan and HPMC, prepared by solvent casting from 0.1 M HCl (pH 1.5) and 0.1 M acetic acid (pH 2.9) were evaluated for their morphological and leaching properties. Films cast at pH 1.5 were uniform with smooth surfaces while films cast at pH 2.9 showed particle aggregation and had rough surfaces due to polyelectrolyte complex (PEC) formation between pectin and chitosan in the medium. The leaching of pectin was higher from films at cast pH 1.5 due to the absence of PEC formation. Pectin leaching was controlled in simulated upper gastrointestinal conditions but was accelerated in the presence of pectinolytic enzymes. The leaching of pectin from the mixed films was a function of the pH of the film casting solvent, pH of the incubation medium, PEC formation and HPMC content.