Grades Of Hydroxypropyl Methylcellulose Research Articles

Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release

Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the gel layer of swollen intact matrix tablets and drug release was investigated. Two sets of quetiapine fumarate (QF) matrix tablets were prepared using the high viscosity grade HPMC K4M at low (70 mg/tablet) and high (170 mg/tablet) polymer concentrations. Viscoelastic studies using a controlled stress rheometer were performed on swollen matrices following hydration in the dissolution medium for predetermined time intervals. The gel layer of swollen tablets exhibited predominantly elastic behavior. Results from the in vitro release study showed that drug release was strongly influenced by the viscoelastic properties of the gel layer of K4M tablets, which was further corroborated by results from water uptake studies conducted on intact tablets. The results provide evidence that the viscoelastic properties of the gel layer can be exploited to guide the selection of an appropriate matrix-forming polymer, to better understand the rate of drug release from matrix tablets in vitro and to develop hydrophilic controlled-release formulations.

Formulation Approach to Improve the Gastric Residence Time of Bisoprolol Fumarate by Gastro-Retentive Tablets

Purpose: Gastric retentive drug delivery devices can be used for controlled drug delivery systems containing drugs, which are degraded in the colon. The main objective of the present study is to design and formulate gastric retentive controlled release dosage form of bisoprolol fumarate in order to improve the gastric residence time, which in turn increases its bioavailability. Approach: Floating dosage form of bisoprolol fumarate was prepared by direct compression method using different concentration and grades of hydroxypropyl methylcellulose and sodium bicarbonate. Prepared powder mixtures and tablets were subjected to various pre-compression and post-compression evaluations respectively. Findings: Powder mixture showed good flow properties for uniform die filling. The SEM analysis showed minimum number of pores and erosion on the surface of the tablet. The optimized formulation F8 gave floating lag time less than 3 min with a floating time of 12 h, and an in vitro release profile very near to the desired release. The prepared dosage form reported to follow the zero order release and non-Fickian mechanism. Best formulations were subjected to accelerated stability studies. The assay results showed that the drug was stable for 3 months without any change in the drug content. Conclusion: Finally it can be concluded that the gastric retentive time of bisoprolol can be increased by formulating it in a floating dosage form.

Hydroxypropylmethyl cellulose‐based sponges loaded self‐microemulsifying curcumin: Preparation, characterization, and in vivo oral absorption studies

ABSTRACTNovel hydroxypropylmethyl cellulose (HPMC)‐based sponges containing self‐microemulsifying curcumin (SME‐Cur) were prepared by a freeze drying method using different grades of HPMC (E5 LV, E15 LV, E50 LV, A15 LV, and A4C). The physical properties and drug release from these carriers were characterized and compared among the different formulations. The mean pore size values of the sponges from image analysis ranged from 43.36 ± 4.54 to 123.22 ± 8.19 nm. An increase in the concentration or viscosity of the HPMC, resulted in denser sponges and a slower drug release. The average microemulsion droplet size from the optimal sponge formulation was 34.80 ± 0.1 nm, and the curcumin was almost completely released within 120 min. The AUC after oral administration of the liquid and solid SME‐Cur were 7‐ and 5‐fold greater than that of the curcumin powder in the rabbit, respectively. The results demonstrated that the HPMC‐based sponges loaded with SME‐Cur could be efficiently used to enhance the oral bioavailability and might be useful as they could be administered at a lower dose compared to normal curcumin powder. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42966.

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions.

Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

To Differentiate End-Point of Wet Granulation for Various Grades of Hydroxypropyl Methylcellulose by Utilizing Thermal and Rheological Approaches

To Differentiate End-Point of Wet Granulation for Various Grades of Hydroxypropyl Methylcellulose by Utilizing Thermal and Rheological Approaches

Preparation and characterization of dipyridamole solid dispersions for stabilization of supersaturation: effect of precipitation inhibitors type and molecular weight

Dipyridamole (DPL) is a weakly basic BCS class II drug which precipitates upon entering into intestine leading to pH dependant and variable absorption. Thus, research envisaged focuses on developing formulations that maintain supersaturation following upon acid to neutral pH transition. In an endeavor to accomplish the objective, solid dispersion (SD) with hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) was prepared by a quench cooling method. The three molecular weight grades of HPMC (HPMC E5, HPMC E15 and HPMC E50) and two molecular weight grades of PVP (PVP K30 and PVP K90) were investigated to observe effect of increasing molecular weight on stabilizing DPL supersaturated solutions. Equilibrium solubility studies revealed increase in solubility with both HPMC and PVP with greater benefit from HPMC. In vitro supersaturated dissolution results demonstrated that HPMC formulations provided greater degree and extent of supersaturation as compared to PVP formulations. The formulation with HPMC E50 provided maximum stabilization to supersaturation upon acid to neutral pH transition. Moreover, the effect of increase in molecular weight was more pronounced in HPMC rather than PVP. Stronger interactions were observed for DPL with HPMC, while no interaction was observed with PVP which was evident from Fourier transform infra-red studies. Differential scanning calorimetry and powder X-ray diffraction studies revealed the amorphous state of DPL in SD.

Continuous manufacturing of extended release tablets via powder mixing and direct compression

The aim of the current work was to explore continuous dry powder mixing and direct compression for manufacturing of extended release (ER) matrix tablets. The study was span out with a challenging formulation design comprising ibuprofen compositions with varying particle size and a relatively low amount of the matrix former hydroxypropyl methylcellulose (HPMC). Standard grade HPMC (CR) was compared to a recently developed direct compressible grade (DC2). The work demonstrate that ER tablets with desired quality attributes could be manufactured via integrated continuous mixing and direct compression. The most robust tablet quality (weight, assay, tensile strength) was obtained using high mixer speed and large particle size ibuprofen and HPMC DC2 due to good powder flow. At low mixer speed it was more difficult to achieve high quality low dose tablets. Notably, with HPMC DC2 the processing conditions had a significant effect on drug release. Longer processing time and/or faster mixer speed was needed to achieve robust release with compositions containing DC2 compared with those containing CR. This work confirms the importance of balancing process parameters and material properties to find consistent product quality. Also, adaptive control is proven a pivotal means for control of continuous manufacturing systems.

Impact of HPMC on the physical properties of spray-congealed PEG microparticles and its swelling effect on rifampicin dissolution

Context: Many active substances are poorly water-soluble and pose a great challenge when orally administered because drug bioavailability is largely dependent on its solubility.Objective: The objective of this investigation was to evaluate the effect of hydroxypropyl methylcellulose (HPMC) as an additive on the physical properties of spray-congealed polyethylene glycol (PEG) microparticles.Materials and methods: The effects of four viscosity grades of HPMC (K100 LV, K4M, K15M and K100M) on the spray-congealing process yield and physical properties of spray-congealed microparticles, such as morphology and particle size, were studied. The swelling effect of HPMC on drug release was also explored using surface plots.Results and discussion: Molten mixtures containing PEG and HPMC of various grades and concentrations were successfully spray-congealed with useful yield ranging from 42.6% to 58.4%. Smooth and spherical microparticles were produced and their size was found to increase with increasing feed viscosity. The swelling extent of microparticles was found to be influenced by the grade, particle size and amount of HPMC present while the rate of erosion depended on the formation of the barrier and grade of HPMC used. Formulations with appropriate rates of erosion were selected to prepare microparticles with rifampicin (RIF), a poorly water-soluble drug. At 10% (w/w), K100 LV was found to enhance the dissolution of RIF while K15M retarded the release.Conclusion: The novel application of HPMC as an additive in spray-congealed PEG microparticles not only affected the physical properties of the microparticles but also modified the drug release by its swelling effect.

Investigating effects of hydroxypropyl methylcellulose (HPMC) molecular weight grades on lag time of press-coated ethylcellulose tablets

The research undertaken exemplifies the effects of hydroxypropyl methylcellulose (HPMC) molecular weight (MW) grades of on lag time of press-coated ethylcellulose (EC) tablets. The formulation comprised an immediate release core (containing prednisone as a model drug) surrounded by compression coating with variegated EC-HPMC blends. Five selected HPMC grades (E5, E15, E50, K100LV and K4M) were explored at three different concentrations (10% w/w, 20% w/w and 30% w/w in outer coat) to understand their effects on lag time and drug release. In vitro drug release testing demonstrated that, with increase in concentration of E5 and E15, up to 30% w/w, the mean lag time decreased progressively; whereas with remaining grades, the mean lag time initially decreased up to 20% w/w level and thereafter increased for 30% w/w level. Importantly, with increase in HPMC concentration in the outer coat, the variability in lag time (%RSD; n = 6) was decreased for each of E5, E15 and E50, whereas increased for K100LV and K4M. In general, the variability in lag time was increased with increase in HPMC MW at studied concentration levels. Markedly, tablets with 30% w/w K4M in outer coat exhibited slight premature release (before the rupture of outer coat) along with high variability in lag time. Overall, the study concluded that low MW HPMCs (E5, E15 and E50) were found rather efficient than higher MW HPMCs for developing robust EC-based press-coated pulsatile release formulations where precise lag time followed by sharp burst release is desired.

In-vitro and in-vivo evaluation of repaglinide loaded floating microspheres prepared from different viscosity grades of HPMC polymer

During the study repaglinide encapsulated floating microspheres were formulated and characterized for enhancing residence time of drug in git and thereby increasing its bioavailability. Floating microspheres of ethylcellulose (EC) and hydroxypropyl methyl cellulose (HPMC) (5 and 100cps) were prepared by emulsion solvent diffusion technique. During process optimization various parameters were studied such as: drug: polymer ratio, polymer ratio, concentration of emulsifier and stirring speed. Selected optimized formulations were studied for SEM, entrapment, floating behavior, drug release and kinetics. In-vivo floating ability (X-ray) study and in-vivo antidiabetic activity were performed on alloxan induced diabetic rats. Microspheres prepared with different viscosity grade HPMC were spherical shaped with smooth surface. Size of microspheres was in the range of 181.1–248μm. Good entrapment and buoyancy were observed for 12h. X-ray image showed that optimized formulation remained buoyant for more than 6h. Optimized formulation treated group shows significant (p<0.01) reduction in blood glucose level as compared to pure drug treated group. Repaglinide loaded floating microspheres expected to give new choice for safe, economical and increased bioavailable formulation for effective management of NIDDM.

Formulation and optimization of mucoadhesive buccal patches of losartan potassium by using response surface methodology.

Background:This study was undertaken with an aim to systematically design a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology (RSM) by employing 32 full factorial design.Materials and Methods:Mucoadhesive buccal patches were prepared using different grades of hydroxypropyl methylcellulose (HPMC) (K4M and K100M) and polyvinylpyrrolidone-K30 by solvent casting method. The amount of the release retardant polymers – HPMC K4M (X1) and HPMC K100M (X2) was taken as an independent variable. The dependent variables were the burst release in 30 min (Y1), cumulative percentage release of drug after 8 h (Y2) and swelling index (Y3) of the patches. In vitro release and swelling studies were carried out and the data were fitted to kinetic equations.Results:The physicochemical, bioadhesive, and swelling properties of patches were found to vary significantly depending on the viscosity of the polymers and their combination. Patches showed an initial burst release preceding a more gradual sustained release phase following a nonfickian diffusion process.Discussion:The results indicate that suitable bioadhesive buccal patches with desired permeability could be prepared, facilitated with the RSM.

Pharmacological Efficacy of Insulin-Loaded Granules Made Up of Various Grades of Hydroxypropyl Methylcellulose in Normal Rats

The aim was to study the potential of various hydroxypropyl methylcellulose (HPMC) grades (K100LV, E50LV, E5LV, E4M, K4M and K100M) in enhancing oral bioavailability of insulin. Enteric coated insulin-loaded-HPMC granules were compared with peroral solution of zinc insulin in glycerine IP (0.788 mg/0.2 ml). Since lowering of blood glucose levels (BGLs) was used as pharmacological response, the area above curve 24 0 AAC was measured as a pharmacokinetic parameter instead of area under curve (AUC) for calculating bioavailability or pharmacological efficacy. In vitro studies showed that insulin release from granules was barred in acidic medium while almost complete release took place in basic medium upto 8h. In vivo studies in normal rats showed a maximum blood glucose reduction by K100LV based insulin-loaded granules, which corresponded to a relative pharmacological efficacy of ~1.4% and absolute pharmacological efficacy of ~0.5%. In contrast, neither control granules nor control (peroral) solution showed a comparable effect. The multiple comparison post-hoc test, least square difference (LSD; at p = 0.05), showed a significant difference of K100LV-, E50LV-, E5LV-, E4M- based insulin-loaded granules from placebo and of K100LV-, E50LV- based insulin-loaded granules from peroral solution. The potential of insulin-loaded HPMC granules followed a general order of K100LV > E50LV > E5LV > E4M > K4M > K100M in lowering of % BGLs. Therefore, low viscosity grades of HPMC are efficient in enhancing oral insulin absorption as compared to high viscosity grades.

Effect of Various Types of Hydroxypropyl Methylcellulose (HPMC) Films on Surface Free Energy and Contact Angle

The aim of this study was to investigate the physicochemical characteristics of various viscosity grades of hydroxypropyl methylcellulose (HPMC) for mucoadhesive buccal films. The HPMC used in this study was K4M, K15M and K100M which their viscosity were 4000, 15000 and 100000 mPas respectively. Using HPMC as film forming base matrix, all intrinsic characteristics of each HPMC grade is required as basic knowledge for the development of mucoadhesive buccal films. To understand the primary essential parameters, surface free energy and contact angle of various HPMC grades were determined. Sessile drop technique was used in this study to determine contact angle of HPMC and surface free energy was then evaluated by using the Wu’s equation. The results showed that the increase in viscosity of HPMC film tended to decrease the polar force and total surface free energy but increased the contact angle. These parameters indicated that the hydrophilic character of HPMC was influenced by its viscosity. Our study suggested that the polar and dispersive force detected by sessile drop technique could be beneficial for the further design and development of mucoadhesive buccal films.

Optimization of Polymer Concentration for Designing of Oral Matrix Controlled Release Dosage Form

Patient’s compliance can be enhanced by using extended release drug delivery systems which allow decreasing the number of daily doses, and helping to maintain uniform drug levels and increase the safety margin for high-potency drugs. Hydroxypropyl methylcellulose (HPMC) is the most commonly used hydrophilic polymer for the preparation of oral controlled drug delivery systems. This research was conducted with the aim of developing matrix based oral controlled release tablets for the drug diclofenac sodium using different viscosity grades of HPMC (K15M) and to compare the drug release characteristics with those of a commercial product, Voltaren® SR 100. Similarity factor (f2), values in between test formulation and marketed preparation was calculated to choose the best formulation. The release kinetics from various matrices was also studied. Increasing in polymer content reduced the rate of drug release. At the same polymer content in the matrix, the drug release was most sustained with tablets prepared using HPMC (K15M). Out of all the formulations studies, matrix tablets containing 40% of HPMC (K15M) showed comparable dissolution profile to that of the marketed preparation as indicated by a similarity factor value of (f2) 88.30%. The release of drug from marketed preparation and matrix with HPMC (K15M) 40% was found to be a diffusion drug mechanism as per Higuchi equation.

Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets

Four different hydrophilic matrix formulations based on hydroxypropyl methylcellulose (HPMC) were investigated for erosion properties in vivo. Three formulations contained a fixed amount of HPMC (40%) with varying proportions of two HPMC grades with different molecular weights (Methocel K100LV and K4M), and a fourth formulation contained a lower amount of the HPMC of lower molecular weight (20%). The effect of food on the in vivo erosion behavior was investigated on two formulations containing different contents of the same HPMC grade. The in vivo erosion behavior and gastrointestinal transit were investigated using magnetic marker monitoring (MMM). The in vitro and in vivo erosion–time profiles show that the erosion was strongly dependent on the composition of the formulation. The formulations containing a larger proportion of high molecular weight HPMC or higher content of HPMC exhibit relatively slower erosion rate and vice versa. In vivo erosion rates were significantly higher under postprandial administration as compared to fasted state administration. No rapid disintegration of any of the formulations (i.e. formulation failure that can potentially cause dose dumping) was observed.

Novel sustained release and swellable gastroretentive dosage form for ciprofloxacin hydrochloride.

Introduction:The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form.Materials and Methods:Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant.Results:The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits.Conclusion:The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants.

Solubility and dissolution enhancement of HPMC ‑ based solid dispersions of carbamazepine by hot‑melt extrusion technique

The objective of this study was to investigate solid dispersions (SDs) of poorly water soluble drug carbamazepine (CBZ), prepared using low viscosity grade hydroxypropyl methyl cellulose (HPMC) (Methocel® E3 LV and Methocel® E5 LV) by hot‑melt extrusion (HME) technology. Saturation solubility and dissolution profile of CBZ was studied. Characterization of hot‑melt extruded samples was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X‑ray diffraction studies (XRD). The result of the study showed the conversion of crystalline form of drug into amorphous form indicating increase in saturation solubility and dissolution rate of CBZ. Key words: Carbamazepine, hot‑melt extrusion, hydroxypropyl methyl cellulose

Drug Release-Modulating Mechanism of Hydrophilic Hydroxypropylmethylcellulose Matrix Tablets: Distribution of Atoms and Carrier and Texture Analysis

Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets.

Enhanced solubility and dissolution of simvastatin by HPMC-based solid dispersions prepared by hot melt extrusion and spray-drying method

The objective of this study was to use low viscosity grade hydroxypropyl methyl cellulose (Methocel® E3 LV and Methocel® E5 LV) to enhance the solubility and dissolution of poorly water soluble drug simvastatin (SIM). Two different technologies, hot melt extrusion and spray drying were employed. Characterization of hot melt extrudes and spray dried samples was done by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies and scanning electron microscopy. The result of the study showed the conversion of crystalline form drug into amorphous form indicating increase in dissolution rate and solubility of SIM.