Hydroxypropyl Methylcellulose K100 Research Articles

Role of various natural, synthetic and semi-synthetic polymers on drug release kinetics of losartan potassium oral controlled release tablets.

Objective:The objective of the present work was to formulate and to characterize controlled release matrix tablets of losartan potassium in order to improve bioavailability and to minimize the frequency of administration and increase the patient compliance.Materials and Methods:Losartan potassium controlled release matrix tablets were prepared by direct compression technique by the use of different natural, synthetic and semisynthetic polymers such as gum copal, gum acacia, hydroxypropyl methyl cellulose K100 (HPMC K100), eudragit RL 100 and carboxy methyl ethyl cellulose (CMEC) individually and also in combination. Studies were carried out to study the influence of type of polymer on drug release rate. All the formulations were subjected to physiochemical characterization such as weight variation, hardness, thickness, friability, drug content, and swelling index. In vitro dissolution studies were carried out simulated gastric fluid (pH 1.2) for first 2 h and followed by simulated intestinal fluid (pH 6.8) up to 24 h, and obtained dissolution data were fitted to in vitro release kinetic equations in order to know the order of kinetics and mechanism of drug release.Results and Discussion:Results of physiochemical characterization of losartan potassium matrix tablets were within acceptable limits. Formulation containing HPMC K100 and CMEC achieved the desired drug release profile up to 24 h followed zero order kinetics, release pattern dominated by Korsmeyer — Peppas model and mechanism of drug release by nonfickian diffusion. The good correlation obtained from Hixson-Crowell model indicates that changes in surface area of the tablet also influences the drug release.Conclusion:Based on the results, losartan potassium controlled release matrix tablets prepared by employing HPMC K100 and CMEC can attain the desired drug release up to 24 h, which results in maintaining steady state concentration and improving bioavailability.

FORMULATION AND DEVELOPMENT OF TRAMODOL HYDROCHLORIDE EXTENDED RELEASE TABLETS

Objective Extended release tablets are considered as a boon to patients suffering from pain as they provide continuous availability of drugs in systemic circulation. Tramadol Hydrochloride is a water soluble opiod analgesic drug which acts centrally by blocking the pain signals sent by the nerves to brain. It is widely accepted as a drug for the treatment of osteoarthritis. Design An attempt was made to prepare Tramadol Hydrochloride extended release matrix tablets by employing various polymers Hydroxy propyl cellulose, Ethyl cellulose, Hydroxy propyl methyl cellulose K100 and Chitosan in combinations to retard the release rates. Direct compression technique was adopted for preparing matrix tablets. Dicalcium phosphate, Magnesium stearate, Colloidal silicon dioxide were used as excipients along with rate retarding polymers. Intervention Precompression and post compression parameters like flow properties, compressibility index, hausner’s ratio, weight variation, hardness, thickness, content uniformity etc., were evaluated by appropriate methods. Invitro dissolution studies were performed to study the rate retarding effects of polymers. Result Formulations containing Hydroxy propyl cellulose and Ethyl cellulose at higher concentration gave very good dissolution profile leading to extended release. Other formulations with various combinations and proportions also retarded the release rate to various levels. Conclusion it is evident that combination of Hydroxy propyl cellulose and Ethy cellulose are suitable polymers for preparing extended release Tramadol Hydrochloride matrix tablets. Also other polymer combinations indicated a promising solution to prepare extended release matrix tablets. Key words Tramadol Hydrochloride, Matrix, Polymer, Extended release, Hydroxy propyl cellulose, Ethyl cellulose, Hydroxy propyl methyl cellulose K100, Chitosan.

Development and in-vivo characterization of novel trans buccal formulations of Amiloride hydrochloride

ObjectivesFormulation development and characterization of novel trans-buccoadhesive patches and bilayer tablets of Amiloride hydrochloride (AMHCL) with the objectives to avoid the first-pass effect, incomplete absorption from GIT, improve the bioavailability, minimize the dose, improve the duration of action and hence produce controlled drug delivery. MethodsAMHCL patches were prepared by solvent casting method, using hydroxy propyl methyl cellulose (HPMC), Carbopol, Chitosan, and polyvinylpyrrolidone-K30 (PVP). Tablets were prepared by direct compression method, using sodium carboxy methyl cellulose (SCMC), HPMC K100, sodium alginate, Carbopol 934 P, Eudragit RL 100, PVP and ethyl cellulose (EC) as a backing layer. The both formulations were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behavior, tensile strength, buccoadhesive strength, surface pH and in vitro release studies. ResultsData of in vitro release from both patches and tablets were fit to different equations and kinetic models to explain release profiles. In vivo drug release studies in rabbits showed 91.65% of drug release from HPMC-Chitosan patch, while it was 82.63–90.21% release from sodium alginate-SCMC buccal tablets. Good correlation among in vitro release and in vivo release of AMHCL was observed in both formulations. ConclusionThe satisfactory results were obtained in all prepared formulations and based on the results, it can be concluded, Amiloride hydrochloride oral mucoadhesive buccal formulations which can be used mainly in minimizing dose and mainly help to improve the patient compliance and Amiloride hydrochloride is a drug of choice for delivery through the control release via buccal route.

Transfersomal lyophilized gel of buspirone HCl: formulation, evaluation and statistical optimization

Context: Buspirone HCl has very low oral bioavailability (4%) due to deactivation by extensive first pass effect. It also has very limited transdermal permeation due to its high hydrophilicity.Objective: The aim of this study was to increase the transdermal permeation of buspirone HCl utilizing a stable dosage form.Methods: Transfersomes were prepared using Tween-80 as a flexibility imparting agent to the vesicular walls. Oleic acid and/or ethanol, with different percentages, were utilized as a permeation enhancer. Formulations were characterized by analyzing particle size, polydispersity index, zeta potential, entrapment efficiency, in vitro release and ex vivo drug permeation. Factorial design (32) was planned for the optimization of formulations using Design-Expert® software. Lyophilized transfersomal gel of the optimized formulation was prepared using hydroxypropyl methylcellulose (HPMC) K100, carboxymethyl cellulose or sodium alginate with or without mannitol as a cryoprotectant. Physical characterization of the transfersomes and the lyophilized gel were carried out using transmission and scanning electron microscopy, respectively.Results: The optimized formulation (T7), containing 35% oleic acid, had the highest desirability value (0.658) with high ex vivo drug flux (43.40 µg/h/cm2) through rat skin when compared with the aqueous drug solution and formula T1 (without oleic acid). The T7 transfersomal gel containing HPMC K100 (G2) had the highest desirability value (0.640) among the lyophilized gel formulations with decreased ex vivo drug flux (38.98 µg/h/cm2) in comparison with the original transfersomal formula (T7).Conclusions: Lyophilized transfersomal gel containing oleic acid was considered as a promising transdermal delivery system for hydrophilic drugs.

Oral buccoadhesive films of ondansetron: Development and evaluation

Introduction:Difficulty or inability in swallowing tablets/capsules during or after chemotherapy is common due to chemotherapy induced nausea and vomiting in patients. Buccoadhesive films of ondansetron hydrochloride were prepared for the prevention and treatment of chemotherapy-induced emesis. Films of varying polymeric composition were prepared in order to facilitate initial as well as prolonged drug release that could take care of acute as well as delayed emesis.Materials and Methods:Mucoadhesive films were prepared using polymers such as hydroxypropyl methylcellulose (HPMC) E5, HPMC K100, and Eudragit® NE 30 D. The effect of concentration of these polymers on physical properties and drug release were studied. All the films were prepared by solvent casting method. In another part of the study, the effect of drug concentration on physical and mucoadhesive properties of film were assessed, keeping the polymer concentration fixed.Results:Films containing HPMC showed good mucoadhesion. Increasing the concentration of Eudragit® NE 30 D in the films retarded drug release and increased residence time, however, reduced mucoadhesion. At a fixed polymer concentration and ratio, films prepared using an increased drug content showed an increased mucoadhesion.Conclusion:Films prepared using HPMC E5 (1000 mg), HPMC K100 (500 mg), and Eudragit® NE 30 D (750 mg) provided initial rapid followed by sustained drug release over a period of 6 h. Given the promising results, the study concluded that the developed buccal films have the potential to release ondansetron required for chemotherapy induced acute and delayed emesis.

Enhancing and Sustaining AMG 009 Dissolution from a Bilayer Oral Solid Dosage Form via Microenvironmental pH Modulation and Supersaturation

Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation, where poorly soluble acidic AMG 009 molecule was intimately mixed and compressed together with a basic pH modifier (e.g., sodium carbonate) and nucleation inhibitor hydroxypropyl methylcellulose K100 LV (HPMC K100 LV), was demonstrated previously. However, not all acidic or basic drugs are compatible with basic or acidic pH modifiers either chemically or physically. The objective of this study is to investigate whether similar dissolution enhancement of AMG 009 can be achieved from a bilayer dosage form, where AMG 009 and sodium carbonate are placed in a separate layer with or without the addition of HPMC K100 LV in each layer. Study results indicate that HPMC K100 LV-containing bilayer dosage forms gained similar dissolution enhancement as matrix dosage forms did. Bilayer dosage forms without HPMC K100 LV benefitted the least from dissolution enhancement.

Formulation and evaluation of floating oral in situ gelling system of amoxicillin.

Purpose. Effective Helicobacter pylori eradication requires delivery of the antibiotic locally in the stomach. High dose of amoxicillin (750 to 1000 mg) is difficult to incorporate in floating tablets but can easily be given in liquid dosage form. Keeping the above facts in mind, we made an attempt to develop a new floating in situ gelling system of amoxicillin with increased residence time using sodium alginate as gelling polymer to eradicate H. pylori. Methods. Floating in situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methyl cellulose K100, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, floating lag time, total floating time, and in vitro drug release. The formulation was optimized using a 32 full factorial design. Dissolution data were fitted to various models to ascertain kinetic of drug release. Regression analysis and analysis of variance were performed for dependent variables. Results. All formulations (F 1–F 9) showed floating within 30 s and had total floating time of more than 24 h. All the formulations showed good pourability. It was observed that concentration of sodium alginate and HPMC K100 had significant influence on floating lag time, cumulative percentage drug release in 6 h and 10 h. The batch F 8 was considered optimum since it showed more similarity in drug release (f 2 = 74.38) to the theoretical release profile. Conclusion. Floating in situ gelling system of amoxicillin can be formulated using sodium alginate as a gelling polymer to sustain the drug release for 10 to 12 h with zero-order release kinetics.

Formulation of topical bioadhesive gel of aceclofenac using 3-level factorial design.

The objective of this work was to develop bioadhesive topical gel of Aceclofenac with the help of response-surface approach. Experiments were performed according to a 3-level factorial design to evaluate the effects of two independent variables [amount of Poloxamer 407 (PL-407 = X1) and hydroxypropylmethyl cellulose K100 M (HPMC = X2)] on the bioadhesive character of gel, rheological property of gel (consistency index), and in-vitro drug release. The best model was selected to fit the data. Mathematical equation was generated by Design Expert® software for the model which assists in determining the effect of independent variables. Response surface plots were also generated by the software for analyzing effect of the independent variables on the response. Quadratic model was found to be the best for all the responses. Both independent variable (X1 and X2) were found to have synergistic effect on bioadhesion (Y1) but the effect of HPMC was more pronounced than PL-407. Consistency index was enhanced by increasing the level of both independent variables. An antagonistic effect of both independent variables was found on cumulative percentage release of drug in 2 (Y3) and 8 h (Y4). Both independent variables approximately equally contributed the antagonistic effect on Y3 whereas antagonistic effect of HPMC was more pronounced than PL-407. The effect of formulation variables on the product characteristics can be easily predicted and precisely interpreted by using a 3-level factorial experimental design and generated quadratic mathematical equations.

Formulation and evaluation of nitrendipine buccal films

A mucoadhesive drug delivery system for systemic delivery of nitrendipine, a calcium channel blocker through buccal route was formulated. Mucoadhesive polymers like hydroxypropylmethylcellulose K-100, hydroxypropylcellulose, sodium carboxymethylcellulose, sodium alginate, polyvinyl alcohol, polyvinyl pyrrolidone K-30 and carbopol-934P were used for film fabrication. The films were evaluated for their weight, thickness, percentage moisture absorbed and lost, surface pH, folding endurance, drug content uniformity, In vitro residence time, In vitro release and ex vivo permeation. Based on the evaluation of these results, it was concluded that buccal films made of hydroxylpropylcellulose and sodium carboxymethylcellulose (5±2% w/v; F-4), which showed moderate drug release (50% w/w at the end of 2 h) and satisfactory film characteristics could be selected as the best among the formulations studied.

Intragastric floating drug delivery system of cefuroxime axetil: In vitro evaluation.

This investigation describes the development of an intragastric drug-delivery system for cefuroxime axetil. The 32 full factorial design was employed to evaluate contribution of hydroxypropyl methyl cellulose (HPMC) K4M/HPMC K100 LV ratio (polymer blend) and sodium lauryl sulfate (SLS) on drug release from HPMC matrices. Tablets were prepared using direct compression technique. Formulations were evaluated for in vitro buoyancy and drug release study using United States Pharmacopeia (USP) 24 paddletype dissolution apparatus using 0.1N HCl as a dissolution medium. Multiple regression analysis was performed for factorial design batches to evaluate the response. All formulations had floating lag times below 2 minutes and constantly floated on dissolution medium for more than 8 hours. It was found that polymer blend and SLS significantly affect the time required for 50% of drug release, percentage drug release at 12 hours, release rate constant, and diffusion exponent (P<.05). Also linear relationships were obtained between the amount of HPMC K100 LV and diffusion exponent as well as release rate constant. Kinetic treatment to dissolution profiles revealed drug release ranges from anomalous transport to case 1 transport, which was mainly dependent on both the independent variables.

Preparation of Theophylline-Hydroxypropylmethylcellulose Matrices Using Supercritical Antisolvent Precipitation: A Preliminary Study

ABSTRACTSeveral controlled release systems of drugs have been elaborated using a supercritical fluid process. Indeed, recent techniques using a supercritical fluid as a solvent or as an antisolvent are considered to be useful alternatives to produce fine powders. In this preliminary study, the effect of Supercritical Anti Solvent process (SAS) on the release of theophylline from matrices manufactured with hydroxypropylmethylcellulose (HPMC) was investigated. Two grades of HPMC (HPMC E5 and K100) as carriers were considered in order to prepare a sustained delivery system for theophylline which was used as a model drug. The characterization of the drug before and after SAS treatment, and the coprecipitates with carriers, was performed by X-ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC). The dissolution rate of theophylline, theophylline-coprecipitates, and matricial tablets prepared with coprecipitates were determined. The physical characterizations revealed a substantial correspondence of the drug solid state before and after supercritical fluid treatment while drug-polymer interactions in the SAS-coprecipitates were attested. The dissolution studies of the matrices prepared compressing the coprecipitated systems showed that the matrices based on HPMC K100 were able to promote a sustained release of the drug. Further, this advantageous dissolution performance was found to be substantially independent of the pH of the medium. The comparison with the matrices prepared with untreated substances demonstrated that matrices obtained with SAS technique can provide a slower theophylline release rate. A new mathematical model describing the in vitro dissolution kinetics was proposed and successfully tested on these systems.

Studies on the Interaction Between Water and (Hydroxypropyl)Methylcellulose

The moisture sorption and desorption profiles of four different viscosity grades of (hydroxypropyl)methylcellulose (HPMC) 2208 (HPMC K100, HPMC K4M, HPMC K15M, and HPMC K100M) of different particle size fractions were analyzed according to the Young and Nelson equations. These equations describe three locations of the sorbed moisture: monolayer adsorption, externally adsorbed moisture, and internally absorbed moisture. The effects of particle size and viscosity grade of HPMC on the three locations of moisture showed that an increase in particle size generally resulted in a reduction in the amount of internal absorption and an increase in the amount of external adsorption. These changes were more apparant for HPMC K100 and HPMC K4M than for the higher viscosity grades. The lowest values of internally absorbed moisture were obtained for HPMC K100M. Changes in tensile strengths, mean yield pressures, and elastic recoveries of HPMC K4M tablets were explained in terms of the changes produced in the internally absorbed moisture and the externally adsorbed moisture. The amounts of nonfreezing and freezing water in samples exposed to moisture were determined from melting endotherms obtained by differential scanning calorimetry. Increases in the water:HPMC ratio resulted in increases in the enthalpies of water melting for the four viscosity grades of HPMC for the <45 and 250–350 µm particle size fractions. The amount of nonfreezable water was unaffected by change in viscosity grade or particle size.

Oxazepam Dissolution Rate from Hydroxypropylmethylcellulose Matrices

The effect of some formulation variables on the release rate of oxazepam from hydroxypropylmethylcellulose (HPMC) has been investigated. The principal factors affecting this parameter were the content and molecular weight of HPMC, and the drug particle size. pH modified the oxazepam solubility; however, the liberation mechanism was not affected. The oxazepam release mechanism from these matrices has been examined. Values of the diffusional exponent n were in the range 0.61–0.74, indicating that the release of drug was controlled by both diffusion and erosion. When the tablets contained 30% HPMC K100 and the oxazepam particle size was 0.210–0.250 mm, near-zero-order kinetics was obtained (n = 0.85), indicating that erosion plays an important role in the oxazepam liberation.

Development and biopharmaceutical evaluations of a new press-coated prolonged-release salbutamol sulphate tablet in man

The aim of the study described was to develop prolonged-release press-coated tablets of salbutamol sulphate from which drug release would increase with time. The bioavailability of the formulation considered best was then studied in man. The tablets, each consisting of a core and a coat, were prepared using a compression-coating technique. Salbutamol sulphate was divided between the core and the coat in the ratio 2:1 or 1 : 2. Different viscosity grades and amounts of hydroxypropylmethylcellulose (HPMC) were used in the coat. When HPMC K100 was used, release of salbutamol sulphate from tablets with 2/3 of the drug in the core increased with time. The release patterns obtained with 1/3 of the drug in the core were biphasic. With other HPMC grades, the release patterns were best described by zero-order kinetics with 2/3 of the drug in the core and square-root-of-time kinetics with 1/3 of the drug in the core. For all formulations, an increase in the amount of HPMC decreased drug release rate. In man the only statistically significant difference in bioavailability parameters between the test formulation and the commercial reference preparation related to C max values.

Formulation of sustained release promethazine hydrochloride tablets using hydroxypropyl-methylcellulose matrices

The effects of some formulation variables on the release rates of promethazine hydrochloride from hydroxypropylmethylcellulose (HPMC) tablet matrices have been investigated. The major controlling factor appeared to be the promethazine: HPMC ratio and a straight-line relationship existed between the Higuchi-type release rate and the reciprocal of the tablet content of HPMC. Increasing the particle size range of promethazine from 45–63 to 500–700 μm only produced a 12% increase in the drug release rate. Variation in compaction pressure from 93 to 1395 MNm −2 and the absence or presence of 0.75% magnesium stearate as lubricant appeared not to modify release rates. The lowest viscosity grade of HPMC used (HPMC K100) gave the highest release rates at constant HPMC: drug ratio. The other three grades (HPMC K4M, K15M and K100M) showed similar release rates despite the variation in their molecular size.

Propranolol hydrochloride and aminophylline release from matrix tablets containing hydroxypropylmethylcellulose

The effect of aminophylline and propranolol hydrochloride release from sustained release tablets containing four grades of hydroxypropylmethylcellulose (HPMC) has been examined. The effect of drug: HPMC ratio and drug particle size on drug release has also been investigated. In all cases a plot of % drug dissolved against √time produced a straight line. Similar release rates were obtained from HPMC K4M, HPMC K15M, and HPMC K100M matrices at similar drug: HPMC ratios, although HPMC K100 matrices gave consistently higher rates at identical drug: HPMC levels. It was found that the major factor controlling drug release was the drug: HPMC ratio; increasing the polymer content decreased the dissolution rate of the drug. A straight line relationship was established between the logarithm of the tablet HPMC content and the logarithm of the release rates ( mg · min −1 2 ), enabling release rates to be predicted for a variety of different drug substances. It has been suggested that this relationship is accounted for by considering that the weight of HPMC directly influences the surface area of the matrix which in turn controls the release rate. Changes in drug particle size insignificantly affected drug release.