Grades Of Hydroxypropyl Methylcellulose Research Articles

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

Abstract 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.

Probing the mechanisms of drug release from hydroxypropylmethyl cellulose matrices.

The transient dynamic swelling and dissolution behavior during drug release from hydroxypropylmethyl cellulose (HPMC) matrices was investigated using fluorescein as a model drug. A new flow-through cell capable of providing a well-defined hydrodynamic condition and a non-destructive mode of operation was designed for this purpose to assess the associated moving front kinetics. The results obtained show a continuous increase in transient gel layer thickness irrespective of the polymer viscosity grade or drug loading. This is attributed to the faster rate of swelling solvent penetration than that of polymer dissolution under the present experimental condition. On the other hand, the observed shrinkage of sample diameter over a longer time period demonstrates that polymer dissolution does indeed occur in HPMC matrices. Further, both the rates of polymer swelling and dissolution as well as the corresponding rate of drug release increase with either higher levels of drug loading or lower viscosity grades of HPMC. For water-soluble drugs, the present results suggest that the effect of HPMC dissolution on drug release is insignificant and the release kinetics are mostly regulated by a swelling-controlled diffusional process, particularly for higher viscosity grades of HPMC.

The influence of substitution type on the performance of methylcellulose and hydroxypropylmethycellulose in gels and matrices

Abstract The characteristics of matrices containing hydroxypropylmethylcellulose (HPMC) grades E4M, F4M or K4M, or methylcellulose A4M have been compared using thermomechanical analysis, differential scanning calorimetry (DSC), laser analysis, cloud points and via the dissolution of a model drug, propranolol hydrochloride, from matrices containing the cellulose ethers and prepared by direct compression. Dissolution rates of propranolol varied according to the drug/cellulose ether ratio within the matrix. Propranolol release from methylcellulose matrices was least affected by this ratio but the performance differences of the three grades of HPMC could not be distinguished. In the absence of drug, matrices containing methylcellulose disintegrated at 37 and 44°C. Water uptakes, as measured by DSC and gel layer thicknesses, were similar for each grade of cellulose ether. Matrices containing HPMC K4M tended to swell to the greatest extent. For all grades, swelling was greater in the axial rather than radial direction. Cloud points provided the best prediction of matrix performance.

Viscosity and Stability Studies of Liquid Pafzaffin Emulsions Prepared by Hydroxypropyl Methylcellulose

AbstractLiquid paraffin-water emulsions were prepared by three viscosity grades of hydroxypropyl methylcellulose (HPMC) polymer which showed pseudoplastic behavior. The viscosity of emulsions increased, but the mean droplet diameter of globules decreased on increasing the concentration of the polymer. On storage at 25°C. the viscosity of emulsions stabilized by low viscosity grade polymers increased. For higher viscosity polymer, the emulsion viscosity initially increased and then decreased slightly on aging. Lower viscosity grade HPMC polymers have higher emulsifying efficiency. whereas higher viscosity grade polymer emulsion is much more stable towards centrifugation.

Dissolution of diclofenac sodium from matrix tablets

Abstract Several parameters were studied for their effect on the dissolution of diclofenac sodium from Voltaren SR and hydroxypropylmethylcellulose (HPMC) based matrix tablets. The results indicate that addition of sodium or potassium chloride to the dissolution medium decreases the solubility of the drug and slows the dissolution rate, with the effect of sodium chloride being greater. The dissolution of the drug was studied in a medium which simulates the changing pH of the pathway followed by the drug as it passes from the stomach to the intestine. Dissolution was found to be inversely related to the rate at which the pH was changed. This may be caused by the deposition of an insoluble drug layer when contact is made with an acid medium. When higher viscosity grades of HPMC are used, slower release rates result. Drug release from Voltaren SR is best described as non-Fickian in an aqueous medium irrespective of whether salt is added; however, a zero-order dependence became evident in pH-changing media. The release of diclofenac sodium from the hydrophilic HPMC matrices follows a non-Fickian transport in all media.

Sustained Release Tablet Formulation for a New Iron Chelator

AbstractSustained release tablet formulations for a new orally active iron chelator (1, 2, dimethyl-3-hydroxy-pyrid-4-one, DMHP or L1) have been developed. Coprecipitates containing DMHP and polymer were prepared and compressed into matrix-type tablets. The dissolution profiles as a function of (1) the type of polymer, and (2) polymer content, were determined. Both Eudragit types (RLPM and RSPM) and all hydroxypropylmethylcellulose (HPMC) grades (E4M, E10M, and K4M) exhibited significant sustained release activity. Above a certain ratio, increase in the polymer concentration did not provide any further decrease in the release rates. All grades of HPMC and both Eudragit RSPM and RLPM showed non-Fickian release kinetics. The role of HPMC and Eudragits in the formulation of a sustained release tablet of a water soluble drug is demonstrated.

Effect of hydroxypropylmethylcellulose on gastrointestinal transit and luminal viscosity in dogs

Effect of hydroxypropylmethylcellulose on gastrointestinal transit and luminal viscosity in dogs

Effect of Hydroxypropylmethylcellulose on Gastrointestinal Transit and Luminal Viscosity in Dogs

The effects of hydroxypropylmethylcellulose on upper gastrointestinal transit, viscosity, and water flux were studied in six dogs fistulated at the proximal duodenum and/or mid-jejunum. Combinations of different grades of hydroxypropylmethylcellulose were prepared as 2% or 3.3% solutions to yield input viscosities of low (approximately 5000 cp at 37 degrees C and 1 s-1), medium (15,000 cp), or high (30,000 cp) viscosity. Hydroxypropylmethylcellulose modified intralumenal viscosity, with a linear relationship existing between input and lumenal viscosity. With regard to transit, the lag time before the onset of chyme recovery increased linearly as a function of luminal viscosity. There was also a pronounced decrease in the first-order emptying rate constant as lumenal viscosity increased from water to low-viscosity hydroxypropylmethylcellulose, but as viscosity was further increased there was little additional change. These results indicate that water-soluble fibers can exert a significant influence on both the lumenal viscosity and the transit profile in the upper gastrointestinal tract.

Glass–Rubber Transitions of Cellulosic Polymers by Dynamic Mechanical Analysis

The glass-rubber transition temperatures (Tg) of several cellulosic polymers [hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC)] have been examined using dynamic mechanical analysis (DMA). The melting temperatures of the above polymers were examined using a hot stage melting point apparatus. The primary Tg of three different grades of HPMC (3, 6, and 15 cps) were determined to be 160, 170, and 175 degrees C, respectively. The primary Tg of the HEC film was determined as 120 degrees C. The HPC film did not indicate a primary Tg. These cellulosic polymers also displayed secondary transitions. Hot stage melting of HPMC and HPC was observed at 225 to 254 degrees C and 190 to 195 degrees C, respectively. The HEC powder did not exhibit a melting temperature, but became darker at temperatures greater than 150 degrees C.

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.

The molecular weight and molecular weight distribution of hydroxypropyl methylcellulose used in the film coating of tablets

The molecular weight and molecular weight distributions of nine grades of hydroxypropyl methylcellulose used in the film coating of tablets have been measured using gel permeation chromatography. With the exception of Pharmacoat 603, there is a high molecular (greater than 5 x 10(5)) component present in all grades ranging from relatively small amounts in grades with low nominal viscosity to relatively large amounts in the 50 mPas grade. The peak molecular weight taken from the distribution curve--an indication of the molecular weight of the main component--could be calculated from the nominal viscosity using the equation. Peak molecular weight = 23.54 x 10(3) (viscosity)0.45. The relationship could also be expressed in the standard form [eta]=KM alpha where M is the peak molecular weight [eta] is the intrinsic viscosity and K and alpha are constants (in this case 9.94 x 10-4 and 1.096 respectively). The wide molecular weight distribution of these samples and the presence of quite high proportions of very low molecular weight (less than 5 x 10(3)) components especially in samples with nominal viscosity designations of less than 15 mPas appears to affect their mechanical properties.

<i>In vitro</i> Release Kinetic Study of Esomeprazole Magnesium from Methocel K15M and Methocel K100 LVCR Matrix Tablets

In the present study esomeprazole sustained release tablet matrix was prepared by utilizing different grades of hydroxypropyl methylcellulose (HPMC) polymers such as Methocel K15M & Methocel K100 LVCR by direct compression method. Different amount of Methocel K15M was used to develop matrix builder in the seven proposed formulations (F1-F7) for the study of release rate retardant effect at 20%, 25%, 30%, 35%, 40%, 45% and 50% of total weight of tablet matrix respectively. The dissolution study of Methocel K15M based tablet matrices of those proposed formulations were carried out in the simulated gastric medium (pH 1.3) for first two hours and then in the simulated intestinal medium (pH 6.8) for 8 hours using USP dissolution apparatus II. The formulation F-5 (40%) and F-6 (45%) met the optimum release rate of esomeprazole for 10h period of in vitro dissolution study. The release kinetics of formulation F-5 and F-6 very closely followed Higuchi kinetic order than first order and zero order kinetics. Similarly Methocel K100 LVCR was used to develop matrix builder in another seven proposed formulations (F8-F14). It was found that formulations F-11 (35%), F-12 (40%) and F-13 (45%) met the desired release rate of esomeprazole for 10h period. The release kinetics of formulation F-11, F-12 and F-13 followed Higuchi kinetic order. Between these two polymers, Methocel K100 LVCR showed better release retardant effect than Methocel K15M. Key words: Esomeprazole, Direct compression, Controlled release, Methocel K15M and Methocel K100 LVCRDOI = 10.3329/dujps.v7i1.1216 Dhaka Univ. J. Pharm. Sci. 7(1): 39-45, 2008 (June) Â

In Vitro Release Kinetic Study of Ciprofloxacin HCl from Methocel K15M CR, Methocel K4M CR and Methocel K4M Premium Matrix Tablets

In the present study Ciprofloxacin HCl sustained release matrix tablet was prepared by utilizing different grades of hydroxypropyl methylcellulose (HPMC) polymers such as Methocel K4M CR, Methocel K4M Premium & Methocel K15M CR by direct compression method. Different amount of Methocel K15M CR was used to develop matrix builder in the three proposed formulations (F1-F3) for the study of release rate retardant effect at 5%, 6%, and 7% of total weight of tablet matrix respectively. The dissolution study of Methocel K15M CR based tablet matrices of those proposed formulations were carried out in the simulated gastric medium (pH 1.3) for 8 hours using USP dissolution apparatus II. Similarly Methocel K4M premium was used to develop matrix builder in another three proposed formulations (F4-F6). It was found that formulations F-4 (15%), F-5 (17%) and F-6 (18.3%) met the desired release rate of Ciprofloxacin HCl for 8hrs period. The release kinetics of formulation F-4, F-5 and F-6 followed Higuchi kinetic order. Again Methocel K4M premium was used for another three proposed formulations (F7-F9). It was found that formulations F-7 (6.7%), F-8 (12.3%) and F-9 (15.6%) met the desired release rate of Ciprofloxacin HCl for 8hrs period. The release kinetics of formulation F-7, F-8 and F-9 followed Higuchi kinetic order. Among these three polymers, Methocel K4M Premium showed better release retardant effect than Methocel K4M CR and Methocel K15M CR. Key Words: Ciprofloxacin HCl; Direct compression; Controlled release; Methocel K15M CR; Methocel K4M CR; Methocel K4M premium.DOI: 10.3329/sjps.v2i1.5814Stamford Journal of Pharmaceutical Sciences Vol.2(1) 2009: 37-43