Grades Of Hydroxypropyl Methylcellulose Research Articles

A protocol for the classification of wet mass in extrusion–spheronization

In this study, a structured protocol for the classification of wet mass in extrusion–spheronization was developed to predict formation and pellet quality.The wet masses of 120 formulae were prepared taking microcrystalline celluloses as pelletization aid and lactose, hydroxypropyl methylcellulose grades, herbal medicines as model drugs. Physical properties of the wet masses such as hardness, adhesiveness, springiness, cohesiveness, chewiness, and resilience were tested, respectively, using a texture analyzer. Particles were produced by spheronization process, and the quality of spherical pellets was also evaluated. Data were analyzed by principal component analysis, factor analysis, and classification analysis.The wet masses could be classified into five groups taking the ratio of hardness to springiness (Ha/Sp) as the first classification index and chewiness, resilience as the second and the third classification index. The wet masses of different classification could correspondingly form the different shapes. So, a new protocol could be devised, for example, if the range of Ha/Sp of the wet masses was 30,992–47,689g, at the same time, the value of chewiness was less than 4842, and the value of resilience was no more than 0.139; it would form spherical pellets under the experimental condition.These results demonstrate that the proposed protocol could be a valuable asset in a formulation development project to assess the physical properties of wet masses and to predict formation and pellet quality. So, the tedious and expensive pre-production (pre-formulation and optimization) work could be considerably reduced.

A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation.Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling agents. The comparative dissolution study for the HPMC-based SR tablet as a test and Detrusitol® SR capsule as a reference was carried out, and the bioequivalence study of the two products was also conducted in human volunteers.Results: The amount of HPMC, the grade of HPMC and the combination ratio of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f2 > 50). Furthermore, the dissolution method and rotation speed showed no effects on the drug release from the two products. The 90% confidence intervals of the AUC0–36 and Cmax ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8–log1.25.Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation was successfully developed, which was bioequivalent to Detrusitol® SR capsule.

Formulation in vitro evaluation of floating tablets of hydroxypropyl methylcellulose and polyethylene oxide using ranitidine hydrochloride as a model drug

The present study was carried out with an objective of preparation and in vitro evaluation of floating tablets of hydroxypropyl methyl cellulose (HPMC) and polyethylene oxide (PEO) using ranitidine hydrochloride as a model drug. The floating tablets were based on effervescent approach using sodium bicarbonate a gas generating agent. The tablets were prepared by dry granulation method. The effect of polymers concentration and viscosity grades of HPMC on drug release profile was evaluated. The effect of sodium bicarbonate and stearic acid on drug release profile and floating properties were also investigated. The result of in vitro dissolution study showed that the drug release profile could be sustained by increasing the concentration of HPMC K15MCR and Polyox WSR303. The formulation containing HPMC K15MCR and Polyox WSR303 at the concentration of 13.88% showed 91.2% drug release at the end of 24 hours. Changing the viscosity grade of HPMC from K15MCR to K100MCR had no significant effect on drug release profile. Sodium bicarbonate and stearic acid in combination showed no significant effect on drug release profile. The formulations containing sodium bicarbonate 20 mg per tablet showed desired buoyancy (floating lag time of about 2 minutes and total floating time of >24 hours). The present study shows that polymers like HPMC K15MCR and Polyox WSR303 in combination with sodium bicarbonate as a gas generating agent can be used to develop sustained release floating tablets of ranitidine hydrochloride.

Development of a HPMC-based controlled release formulation with hot melt extrusion (HME)

The objective of this study was to develop hydroxypropyl methylcellulose (HPMC) based controlled release (CR) formulations via hot melt extrusion (HME) with a highly soluble crystalline active pharmaceutical ingredient (API) embedded In the polymer phase. HPMC is considered a challenging CR polymer for extrusion due to its high glass transition temperature (Tg), low degradation temperature, and high viscosity. These problems were partially overcome by plasticizing the HPMC with up to 40% propylene glycol (PG). Theophylline was selected as the model API. By using differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), dynamic mechanical analysis (DMA), and X-ray powder diffraction (XRPD), the physical properties of the formulations were systematically characterized. Five grades of HPMC (Methocel®) – E6, K100LV, K4M, K15M, and K100M – were tested. The extrusion trials were conducted on a 16 mm twIn screw extruder with HPMC/PG placebo and formulations containing theophylline/HPMC/PG (30:42:28, w/w/w). The dissolution results showed sustained release profiles without burst release for the HPMC K4M, K15M, and K100M formulations. The extrudates have good dissolution stability after being stressed for 2 weeks under 40°C/75% RH open dish conditions and the crystalline API form did not change upon storage. Overall, the processing windows were established for the HPMC based HME-CR formulations.

Behaviour of HPMC compacts investigated using UV-imaging

The aim of the study was to visualize the behaviour of the hydroxypropyl methylcellulose (HPMC) in a buffer solution using UV imaging. The obtained results were related to rheological measurements in order to gain insight into critical polymer properties affecting drug release. Two viscosity grades of HPMC, 15cP and 50cP, were used. The behaviour of the polymer at the surface of the compact was observed by UV-imaging at 214nm for 90min in a stagnant buffer solution and in presence of flow. Steady shear and oscillatory shear measurements were conducted to determine the rheological characteristics.Three distinctive phases could be detected by real-time UV-imaging of the HPMC; gel formation due to water penetration, further expansion of the gel into solution and finally steady conditions, where a critical polymer concentration that can withstand the shear forces without eroding was observed. The critical concentration corresponded to the rheologically determined gel point, which is the lowest concentration where a 3D-network is obtained. Higher viscosity grade HPMC swelled more rapidly and lead to a thicker gel layer, which was more resistant towards the shear forces due to the applied flow. The results showed that UV imaging is suitable for obtaining both qualitative and quantitative information on polymer behaviour.

Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil

The purpose of this investigation was to design and develop gastroretentive dosage form for cefuroxime axetil using floating tablet approach with various grades of hydroxypropyl methyl cellulose. Cefuroxime axetil is known to have low bioavailability, short half-life and is absorbed largely from upper GIT. Sodium bicarbonate was used in the dosage form as a source of carbon-di-oxide to maintain buoyancy. In vitro dissolution study results indicated non-Fickian diffusion controlled drug release mechanism and was best fitted into Korsmeyer–Peppas equation. In vivo radiographic studies conducted in five healthy human volunteers for optimized formulation indicated over 6h retention of tablet in the stomach region. Reproducible physical parameters indicated that the current formulation could be easily scaled-up.

Statistical design of experiments on fabrication of bilayer tablet of narrow absorption window drug: Development and In vitro characterisation

The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm2, respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet.

The influence of HPMC viscosity as FRC parameter on the release of low soluble drug from hydrophylic matrix tablets

The importance of functionality-related characteristics (FRC) of hydroxypropyl methylcellulose (HPMC) described in the pharmacopeia monograph can be evaluated only for selected formulation or technological process. The aim of our work was to investigate the influence of apparent viscosity as one of the FRC for two batches of the same HPMC grade on the release properties of diclofenac sodium from HPMC matrix tablets. Our results show that two batches of HPMC differ in viscosity significantly and as a consequence, the significant differences were observed in the release profiles as well. HPMC-B sample has higher viscosity and therefore higher average molecular weight, thus the erosion and drug release were slower compared to HPMC-A sample with lower apparent viscosity. It can be concluded that batch-to-batch viscosity variation of the same HPMC grade can lead to the different release profiles; therefore the specification limits of some FRC should be postulated during the development of each individual formulation. However, the viscosity interval as FRC can not be generalized, because it is different for different tablet compositions.

Thermo-physical characterization of Pharmacoat® 603, Pharmacoat® 615 and Mowiol® 4-98

Hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) are important polymers in pharmaceutical, food and other industries being largely used as encapsulation agents. The characterization of two reference grades of HPMC (Pharmacoat® 603 and Pharmacoat® 615) and one reference grade of PVA (Mowiol® 4-98), through X-ray diffraction (XRD) and thermogravimetry (TG) is described. Specific analyses were performed by means of dynamic vapour sorption analysis of water adsorption/desorption from vapours at 10, 25, 40, 55 and 70 °C. Guggenheim–Anderson–de Boer (GAB), Brunauer–Emmett–Teller (BET), Park and n-layer BET models were successfully used to fit the experimental data. The glass transition temperature as function of water content was measured by means of differential scanning calorimetry (DSC). The experimental data were analysed according to Linear, Gordon–Taylor, Fox and Roos equations. XRD studies revealed amorphous structure for the Pharmacoat® 603 and Pharmacoat® 615 and crystalline for Mowiol® 4-98. Single and multi-step temperature degradation point was found for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98, respectively. The water uptake is higher for Pharmacoat® 603 and Pharmacoat® 615 than Mowiol® 4-98. The influence of temperature on water uptake is opposite for the two types of polymers. GAB and n-layer BET were found to better model Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98 data, respectively. The water makes the glass transition to decrease quite drastically. Gordon–Taylor is better fitting the experimental data both for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98.

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.

Mucoadhesive buccal films of glibenclamide: Development and evaluation

Background:Glibenclamide is an oral hypoglycemic drug completely metabolized in the liver, the principal metabolite being very weakly active, buccal delivery may be useful for the treatment of diabetes more effectively. The aim of the present study was to design formulations and systematically evaluate in vitro and ex vivo performances of buccal films of glibenclamide so that the required therapeutic plasma concentrations can possibly be achieved more rapidly using the different grades of hydroxypropyl methyl cellulose (HPMC) as the base matrix.Materials and Methods:Mucoadhesive buccal films of glibenclamide were prepared by solvent casting technique using different grades of HPMC with different ratios. Prepared films were evaluated for weight, thickness, surface pH, swelling index (SI), folding endurance, drug content uniformity, in vitro release, and ex vivo permeation studies.Results:The film thickness and weight were in the range of 0.213–0.4892mm and 22.25–39.83 mg, respectively. The films exhibited controlled release over more than 6 h. HPMC, HPMCK100, and HPMC3000 films exhibited satisfactory swelling. Surface pH of buccal films was found to be 6.4–6.8. SI observed to be highest for GF12 (275.3 ± 12.17) and lowest for GF1 (173.5 ± 5.65). The films exhibited controlled release over more than 6 h. HPMC exhibited satisfactory swelling, an optimum residence time, and promising drug release. The Higuchi plots were found to be linear with correlation coefficient values of 0.8933, 0.9138, and 0.9947 for GF4, GF8, and GF9, respectively.Conclusions:Among all the formulations, GF9 shows good controlled release results correlated with ex vivo permeation studies.

Evaluation of Hydroxypropyl Methylcellulose Matrix Systems as Swellable Gastro-Retentive Drug Delivery Systems (GRDDS)

Utilizing gastro-retentive drug delivery systems (GRDDS) to increase absorption of weakly basic drugs by extending their transit time is a promising approach. Swellable systems were evaluated for this purpose. Such systems demonstrate dual mechanism of release-diffusion and erosion. GRDDS requires maintaining its dimensions, which demands diffusion as a predominant mechanism of release (Fickian). In this work, dypyridamole, a weakly basic drug, together with various grades of hydroxypropyl methylcellulose and different excipients were evaluated for release and swelling properties. Dissolution data were analyzed by curve fitting to various models to estimate predominant release mechanism. It was found that matrices containing a swellable diluent like microcrystalline cellulose demonstrated predominantly Fickian mechanism of release, whereas soluble diluents (lactose and mannitol) contributed to a mixed mechanism of release. Addition of copovidone increased the swelling and survivability, whereas sodium chloride altered the erosion behavior. A correlation between matrix weight loss and drug release was obtained, which further consolidated the analysis. Correlation for the soluble excipients was linear, whereas that for the swellable excipient was nonlinear, implying predominance of Fickian release mechanism for the latter. Hence, the selection of excipients can influence matrix survivability and release kinetics, which can be used for developing GRDDS.

Repeated impacts tests and nanoindentation as complementary tools for mechanical characterization of polymer‐coated particles

AbstractPolymer‐coated particles have been produced by applying two grades of hydroxypropyl methylcellulose and one grade of polyvinyl alcohol onto sodium benzoate Purox‐S core particles by using top‐spray fluid bed coater and then stored under two different conditions, namely ambient conditions (23°C, 55% RH) and in the freezer (−18°C, 25% RH). Surface morphology has been firstly analyzed using scanning electron microscope and atomic force microscope. Resistance to attrition and viscoelastic properties have been measured by repeated impact tester (RIT) and nanoindentation, respectively. The resistance to attrition have been discussed as function of type of coating materials, breakage mechanisms, and storage temperature, and then compared with uncoated Purox‐S. The storage conditions is not influencing the morphology, whereas is strongly affecting the resistance to attrition. Coated particles stored at −18°C were found to be more resistant to attrition than ones stored at room conditions. Such differences negligible at low energies (low numbers of impacts) increase as soon as the number of impacts and the energy rise. The improvement in the resistance to attrition was related to the plasticizing effect of water content. Displacement, storage modulus (E′), loss modulus (E″), and damping factor (tan δ) have been measured for all coated particles. Quasistatic and dynamic nanoindentation were found to agree very well with each other. Comparison of the nanoindentation results and the RIT results showed that tan δ, as measure of viscoelasticity and flexibility of the polymeric coating material, is related to the attrition behavior. It was found, in fact, that a higher tan δ gives more resistance to attrition. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010

Characterization of physical and viscoelastic properties of polymer films for coating applications under different temperature of drying and storage

The increasing tendency to enhance consumer products with added functionality is leading to ever more complex products. Nowadays more and more particulate products are coated to give the product specific functionalities. An appropriate approach is needed to be able to satisfy customer's requirements. In this work, three reference well-known coating agents, namely two grades of hydroxypropyl methylcellulose (HPMC) and one polyvinyl alcohol (PVA) were selected and investigated. Aqueous solutions of such polymers were obtained and viscosity and shear stress were measured function of shear rate, temperature and polymer concentration. The viscosities of the solutions appear to be mainly shear rate independent, they clearly show Newtonian behaviour. Drying and storage conditions influence on morphology and structure of the cast films were evaluated using scanning electron microscope (SEM). Dynamic mechanical thermal analysis (DMTA) experiments were carried out on HPMC and PVA cast films to assess the viscoelastic properties over wide temperature–frequency range. The time–temperature superposition principle was used to determine the shift factor, a T , and to compose a master curve. Magnitudes and profiles of storage modulus, E′, loss modulus, E″, and tan δ master curves are discussed with relation to drying and storage conditions. No impact of drying temperature on the polymer properties was observed whereas the effect of storage temperature resulted to be relevant in terms of shifts in glass transition temperature and, only partially, changes in the magnitudes of E′ and E″.

Bio-fluid uptake and release of Indomethacin of direct-compressed HPMC tablets

Tablets of three different grades of hydroxypropyl methyl cellulose (HPMC), having different viscosity, were prepared using the direct-compression technique with no additive or binder. The fluid uptake behavior of these HPMC tablets was studied in three types of bio-media – water, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF). The amount of fluid uptake by the tablets followed a power law relationship with time for all three media. Variants such as pH value, type of salts and salt concentration in the media were found to have little influence on the swelling process for the tablet. On the contrary, viscosity and molecular weight of HPMC were the controlling parameters for the swelling process. Subsequently, Indomethacin was added in certain percentage to the tablets as a model drug. It was to examine and elucidate drug releasing properties of the HPMC tablets. The possible mechanisms involved in the process of drug dispersion are proposed and discussed.

Application of percolation theory in the study of an extended release Verapamil hydrochloride formulation

The percolation theory studies the critical points or percolation thresholds of the system, where one component of the system undergoes a geometrical phase transition, starting to connect the whole system. The objective of the present paper was to study the existence of critical points governing the water and drug transport inside hydroxypropylmethylcellulose (HPMC) hydrophilic matrix systems obtained with different polymer viscosity grades. For this purpose, extended release formulations of Verapamil HCl, have been prepared and studied. The percolation theory has been applied for the first time to multi-component hydrophilic matrices. The materials used to prepare the tablets were Verapamil HCl, four different viscosity grades of HPMC, microcrystalline cellulose, lactose, magnesium stearate and colloidal silicon dioxide NF. In order to estimate the percolation threshold, the behaviour of the kinetic parameters with respect to the volumetric fraction of each component at time zero, was studied. From the point of view of the percolation theory, the optimum concentration for all the studied polymers, to obtain a hydrophilic matrix system for the controlled release of Verapamil HCl is higher than 20% (v/v) HPMC. Above 20% (v/v) HPMC, an infinite cluster of excipient would be formed, ensuring uniform hydration, maintaining integrity of the system and controlling the drug release.

Evaluation of injection moulding as a pharmaceutical technology to produce matrix tablets

The aim of this study was to develop sustained-release matrix tablets by means of injection moulding and to evaluate the influence of process temperature, matrix composition (EC and HPMC concentration) and viscosity grade of ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) on processability and drug release. The drug release data were analyzed to get insight in the release kinetics and mechanism. Formulations containing metoprolol tartrate (30%, model drug), EC with dibutyl sebacate (matrix former and plasticizer) and hydrophilic polymer HPMC were extruded and subsequently injection moulded into tablets (375 mg, 10 mm diameter, convex-shaped) at temperatures ranging from 110 to 140 °C. Tablets containing 30% metoprolol and 70% ethylcellulose (EC 4 mPa s) showed an incomplete drug release within 24 h (<50%). Increasing production temperatures resulted in a lower drug release rate. Substituting part of the EC fraction by HPMC (HPMC/EC-ratio: 20/50 and 35/35) resulted in faster and constant drug release rates. Formulations containing 50% HPMC had a complete and first-order drug release profile with drug release controlled via the combination of diffusion and swelling/erosion. Faster drug release rates were observed for higher viscosity grades of EC (Mw > 20 mPa s) and HPMC (4000 and 10,000 mPa s). Tablet porosity was low (<4%). Differential scanning calorimetry (DSC) and X-ray powder diffraction studies (X-RD) showed that solid dispersions were formed during processing. Using thermogravimetrical analysis (TGA) and gel-permeation chromatography no degradation of drug and matrix polymer was observed. The surface morphology was investigated with the aid of scanning electron microscopy (SEM) showing an influence of the process temperature. Raman spectroscopy demonstrated that the drug is distributed in the entire matrix, however, some drug clusters were identified.

Formulation and In Vitro Studies of a Fixed-Dose Combination of a Bilayer Matrix Tablet Containing Metformin HCl as Sustained Release and Glipizide as Immediate Release

The emerging new fixed dose combination of metformin hydrocholride (HCl) as sustained release and glipizide as immediate release were formulated as a bilayer matrix tablet using hydroxy propyl methyl cellulose (HPMC) as the matrix-forming polymer, and the tablets were evaluated via in vitro studies. Three different grades of HPMC (HPMC K 4M, HPMC K 15M, and HPMC K 100M) were used. All tablet formulations yielded quality matrix preparations with satisfactory tableting properties. In vitro release studies were carried out at a phosphate buffer of pH 6.8 with 0.75% sodium lauryl sulphate w/v using the apparatus I (basket) as described in the . The release kinetics of metformin were evaluated using the regression coefficient analysis. There was no significant difference in drug release for different viscosity grade of HPMC with the same concentration. Tablet thus formulated provided sustained release of metformin HCl over a period of 8 hours and glipizide as immediate release.

In vivo evaluation of nitrofurantoin floating solid drug delivery system

The aim of the present study was to describe the in vivo performance and pharmacokinetic parameters of formulated floating tablets and capsules containing nitrofurantoin, different grades of hydroxypropyl methylcellulose (HPMC) and a gas generating agent. The bioavailability study was performed on six human volunteers using HPLC analysis of urine samples and was compared with non-floating commercial capsules of the drug. The results showed that the floating formulations were capable of maintaining therapeutic urinary levels up to 12 h with a higher extent of recovered unchanged drug (45.46-56.45 mg). The relative bioavailability of floating formulations calculated from the total area under the urinary excretion rate-time curve (AUC 0 -24 ) was found to be increased about 1.66-2.06 times in comparison to the marketed capsules. In vitro-in vivo correlation was done by relating the cumulative percent dissolved to the cumulative percent excreted in urine and a good linear correlation was found. None of the human volunteers who administered the floating formulations exhibited any adverse effects characterized by the pure nitrofurantoin.

A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling

This investigation is aimed at characterization of the mode of release from two different substitution types of HPMC and the effect of chemical structure of drugs using the QSPR (Quantitative - Structure-Property Relationship) technique. To this end, release profiles of HPMC matrices of several drugs containing the same formulation and compressed at a constant pressure were studied. QSPR method was used to establish statistically significant relationships between release parameters and the structural descriptors. Structural descriptors consisted of molecular mechanical, quantum mechanical and graph-theoretical parameters, as well as the partition coefficient and the aqueous solubility of the drugs. The results showed that the most important factors determining the release profile from both HPMC K4M and HPMC E4M matrices were the aqueous solubility of drugs (which could be substituted efficiently by dipole moment) and the size of the drug molecules. Comparison of drug release from matrices prepared using the two grades of HPMC showed very distinct differences for some drugs, as evaluated by the similarity factor. The results indicated that the source of the difference could be sought in the drug properties (as exemplified by the aqueous solubility and surface area) as well as the rate of erosion (that depends mainly on the polymer type).