Amount Of Hydroxypropyl Methylcellulose Research Articles

Influence of Hydroxypropylmethylcellulose and Sodium Lauryl Sulfate on the Solubility and Dissolution of Sirolimus in Solvent‐evaporated Solid Dispersions

The object of this study was to investigate the influence of hydroxypropylmethylcellulose (HPMC) and sodium lauryl sulfate (SLS) on the solubility, dissolution, and crystallinity of poorly water‐soluble sirolimus in solvent‐evaporated solid dispersions. For the selection of suitable carriers, the influence of carriers on the solubility of sirolimus was identified. Among the carriers tested, HPMC and SLS gave most improved drug solubility, resulting in selecting them as a suitable polymer and surfactant, respectively. Numerous solvent‐evaporated solid dispersions were prepared with various ratios of sirolimus, SLS, and HPMC via the spray‐drying system. Then, their aqueous solubility, dissolution, and crystallinity were evaluated. All generated formulations significantly enhanced the solubility and dissolution of drug when compared with the sirolimus powder. As the amount of HPMC and SLS were increased, the solubility and dissolution in solvent‐evaporated solid dispersions were increased. Moreover, all the solid dispersions represented the amorphous form of drug. Among the solid dispersions evaluated, the solid dispersion consisted of sirolimus, HPMC, and SLS at the weight ratio of 1:5:0.1 had most improved aqueous solubility (350.83 ± 11.92 vs. 0.003 ± 0.001 μg/mL) and dissolution (12.58 ± 1.31 vs. 1.13 ± 0.60%, at 240 min) compared with drug powder, respectively. This solvent‐evaporated solid dispersion appeared as the round‐shape and reduced the particle sizes. Thus, HPMC and SLS considerably affected the solubility and dissolution. Furthermore, this novel solvent‐evaporated solid dispersion would be a potential candidate for oral preparation of sirolimus.

A trade-off between solubility enhancement and physical stability upon simultaneous amorphization and nanonization of curcumin in comparison to amorphization alone

The numerous health benefits of curcumin (CUR) have not been fully realized due to its low aqueous solubility, resulting in poor bioavailability. While amorphization of CUR via amorphous solid dispersion (ASD) represents a well-established CUR solubility enhancement strategy, simultaneous amorphization and nanonization of CUR via amorphous CUR nanoparticles (or nano-CUR in short) have emerged only recently as the plausibly superior alternative to ASD. Herein we examined for the first time the amorphous nano-CUR versus the ASD of CUR in terms of their (1) in vitro solubility enhancement capability and (2) long-term physical stability. The ASD of CUR was prepared by spray drying with hydroxypropylmethylcellulose (HPMC) acting as crystallization inhibitor. The amorphous nano-CUR was investigated in both its (i) aqueous suspension and (ii) dry-powder forms in which the latter was prepared by spray drying with adjuvants (i.e. HPMC, trehalose, and soy lecithin). The results showed that the amorphous nano-CUR (in both its aqueous suspension and dry-powder forms) exhibited superior solubility enhancement to the ASD of CUR attributed to its faster dissolution rates. This was despite the ASD formulation contained a larger amount of HPMC. The superior solubility enhancement, however, came at the expense of low physical stability, where the amorphous nano-CUR showed signs of transformation to crystalline after three-month accelerated storage, which was not observed with the ASD. Thus, despite its inferior solubility enhancement, the conventional ASD of CUR was found to represent the more feasible CUR solubility enhancement strategy.

Development of a Video-Microscopic Tool To Evaluate the Precipitation Kinetics of Poorly Water Soluble Drugs: A Case Study with Tadalafil and HPMC.

Many drug candidates today have a low aqueous solubility and, hence, may show a low oral bioavailability, presenting a major formulation and drug delivery challenge. One way to increase the bioavailability of these drugs is to use a supersaturating drug delivery strategy. The aim of this study was to develop a video-microscopic method, to evaluate the effect of a precipitation inhibitor on supersaturated solutions of the poorly soluble drug tadalafil, using a novel video-microscopic small scale setup. Based on preliminary studies, a degree of supersaturation of 29 was chosen for the supersaturation studies with tadalafil in FaSSIF. Different amounts of hydroxypropyl methyl cellulose (HPMC) were predissolved in FaSSIF to give four different concentrations, and the supersaturated system was then created using a solvent shift method. Precipitation of tadalafil from the supersaturated solutions was monitored by video-microscopy as a function of time. Single-particle analysis was possible using commercially available software; however, to investigate the entire population of precipitating particles (i.e., their number and area covered in the field of view), an image analysis algorithm was developed (multiparticle analysis). The induction time for precipitation of tadalafil in FaSSIF was significantly prolonged by adding 0.01% (w/v) HPMC to FaSSIF, and the maximum inhibition was reached at 0.1% (w/v) HPMC, after which additional HPMC did not further increase the induction time. The single-particle and multiparticle analyses yielded the same ranking of the HPMC concentrations, regarding the inhibitory effect on precipitation. The developed small scale method to assess the effect of precipitation inhibitors can speed up the process of choosing the right precipitation inhibitor and the concentration to be used.

Investigation of Effect of Non-Ionic Stabilizers on the Physical Stability of Drug Nanosuspension Prepared By Bottom Up Approach

In this research work, the effects of nonionic stabilizers on the physical stability of drug nanosuspensions were investigated. For this purpose five nonionic polymers (hydroxypropylmethyl cellulose (HPMC), Hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP) and pluronic F68) and esomeprazole were selected as stabilizers and drug candidate, respectively. All the nanosuspensions were prepared using bottom up approach. The potential of Ostwald ripening for the nanosuspensions was investigated by subjecting them to various stress conditions such as storage at various temperature conditions (15°C, 25°C, 35°C, 45°C), mechanically shaking for 72 hours and fluctuation in storage temperature. All the polyvinylpyrrolidone and hydroxypropyl cellulose based formulations that were stored under different stress conditions exhibited the increase in particle size. In other cases the highest increase in mean particle size was observed at 45oC, followed by 35°C. Samples stored at 15°C and 25°C did not exhibit the significant changes in particle size. The HPMC 1 formulation stored at 45°C, exhibited a steep increase in particle size, probably due to desolvation of the HPMC molecules at this temperature and subsequent loss of stabilization of the nanoparticles. However, in case of HPMC 2 and HPMC 3 formulations (stored at 45°C), the gradual increase in particles size was obtained. This trend of increase in particle size was attributed to presentation of excess amount of HPMC. Powder X-ray diffraction analysis confirmed that all the prepared nanosuspensions were in crystalline state. Hence, physical treatments and other factors did not change the crystalline state of nanosuspensions. To Confirm the crystalline state of those samples which were undergo for 3 cycles of temperature fluctuation, the DSC (Differential scanning calorimetry) analysis was performed, and compare with raw drug. Esomeprazole exhibited the melting endotherm at an onset temperature of 178.1°C and a peak temperature at 185.31°C. The thermogram revealed that crystalline state of raw drug was not changes but the melting peak drifted slightly due to presence of stabilizers.

Optimization of Melatonin Dissolution from Extended Release Matrices Using Artificial Neural Networking.

Efficacy of melatonin in treating sleep disorders has been demonstrated in numerous studies. Being with short half-life, melatonin needs to be formulated in extended-release tablets to prevent the fast drop of its plasma concentration. However, an attempt to mimic melatonin natural plasma levels during night time is challenging. In this work, Artificial Neural Networks (ANNs) were used to optimize melatonin release from hydrophilic polymer matrices. Twenty-seven different tablet formulations with different amounts of hydroxypropyl methylcellulose, xanthan gum and Carbopol®974P NF were prepared and subjected to drug release studies. Using dissolution test data as inputs for ANN designed by Visual Basic programming language, the ideal number of neurons in the hidden layer was determined trial and error methodology to guarantee the best performance of constructed ANN. Results showed that the ANN with nine neurons in the hidden layer had the best results. ANN was examined to check its predictability and then used to determine the best formula that can mimic the release of melatonin from a marketed brand using similarity fit factor. This work shows the possibility of using ANN to optimize the composition of prolonged-release melatonin tablets having dissolution profile desired.

Effect of Common Excipients on the Oral Drug Absorption of Biopharmaceutics Classification System Class 3 Drugs Cimetidine and Acyclovir

The objective was to assess the impact of larger than conventional amounts of 14 commonly used excipients on Biopharmaceutics Classification System (BCS) class 3 drug absorption in humans. Cimetidine and acyclovir were used as model class 3 drugs across three separate four-way crossover bioequivalence (BE) studies (n = 24 each) in healthy human volunteers, denoted as study 1A, 1B, and 2. In study 1A and 1B, three capsule formulations of each drug were manufactured, collectively involving 14 common excipients. Capsule formulations that incorporated hydroxypropyl methylcellulose (HPMC) or magnesium stearate exhibited lower absorption. The cimetidine commercial solution contained sorbitol and also resulted in lower absorption. Hence, in study 2, two capsule formulations with lower amounts of HPMC and magnesium stearate, the sorbitol-containing commercial solution, and a sorbitol-free solution were assessed for BE. Overall, 12 common excipients were found in large amounts to not impact BCS class 3 drug absorption in humans, such that these excipients need not be qualitatively the same nor quantitatively very similar to reference, but rather simply be not more than the quantities studied here. Meanwhile, for each HPMC and microcrystalline cellulose, BCS class 3 biowaivers require these two excipients to be qualitatively the same and quantitatively very similar to the reference.

Formulation and Evaluation of Dexibuprofen Transdermal Films in Rabbits

Dexibuprofen is a practically water-insoluble nonsterodial anti-inflammatory drug. Following previous experience on enhancing the solubility of the drug, a mixed hydrotropic solubilization technique was here applied in order to improve the aqueous solubility of the drug so that a soluble form of dexibuprofen was prepared and then could be used as a main active ingredient in transdermal films. Nine formulae were prepared applying 32 full factorial design using different amounts of hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone K30 (PVP K30). The prepared formulae were evaluated for their physical properties, loading efficacy and In-vitro dissolution studies adopting the USP XXII dissolution method type V paddle over disk apparatus method. Permeation studies were done for best three films showing higher dissolution rate using Franz cell apparatus and also bioavailability study was carried out on the best formula to compare the absorption of dexibuprofen from the prepared film (treatment A) to commercial tablets (treatment B) following administration of a single dose to rabbits. The prepared films were off-white color, opaque, smooth, moist and non-sticky. Increasing the amounts of HPMC and PVP K30 lead to increasing weight, folding endurance, tensile strength, moisture content and moisture absorption. Transdermal films containing higher concentrations of PVP K30 and lower concentration of HPMC showed higher rate and amount of dexibuprofen released from dissolution medium and Franz cell. The bioavailability study showed that (Tmax) in treatments A and B is 3 hours and 2 hours respectively. The average peak plasma concentration values (Cmax) were 28.98±3.36 and 34.67±0.61 ug/mL, respectively and the AUC0-∞ values were 145.82±13.09 and 117.44±3.15 µg·h/mL, respectively. There were significant differences between treatments A and B in Cmax, t(1/2)ab, Kel, t(1/2)el, TCR, AUC0-8, AUC0-∞, AUMC0-8, AUMC0-∞, and MRT. While the difference was insignificant in Kab.

Design and Evaluation of Buccal Patch Containing Combination of Hydrochlorothiazide and Lisinopril

Purpose: The objective of the present study was to formulate and evaluate buccal patches containing combination of lisinopril (LP) and hydrochlorothiazide (HCZ). Approach: Films were fabricated by solvent casting method, using combination of mucoadhesive polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA) and polyvinyl pyrolidone (PVP) and ethyl cellulose (EC) as backing layer. The patches were evaluated for physicochemical characteristics such as weight, thickness, surface pH, folding endurance, bioadhesive strength, swelling index, drug content, tensile strength, elongation at break, mucoadhesion time, in vitro and ex vivo drug permeation. Results: The IR spectra showed no interaction between drug and polymer. Physicochemical characteristics of all the samples were found to be satisfactory. Swelling of the films increased with increasing content of HPMC or HPC and PVP. Bioadhesive force, tensile strength, percentage elongation and mucoadhesion time increased with higher proportions of HPMC, HPC and PVA. In vitro drug release studies demonstrated slower release of both drugs in formulations with higher amount of HPMC, HPC and PVA. The in vitro drug release data of most formulations best fitted first order model, except for the formulations FA3 and FC. Ex vivo drug permeation studies of formulations through porcine buccal mucosa showed similar results as in vitro. Conclusion: Buccal delivery of this combination can resolve the drawbacks like incomplete absorption in the gut thereby possible improvement in bioavailability, apart from controlled release of the drugs.

Development of a Robust Method for Simultaneous Quantification of Polymer (HPMC) and Surfactant (Dodecyl β-D-Maltoside) in Nanosuspensions.

This report describes the development of a chromatographic method for the simultaneous quantification of a polymer, hydroxypropyl methylcellulose (HPMC), and a surfactant, dodecyl β-D-maltoside (DM), that are commonly used in the physical stabilization of pharmaceutical formulations such as nanosuspensions and solid dispersions. These excipients are often challenging to quantify due to the lack of chromophores. A reverse phase size exclusion chromatography (SEC) with evaporative light scattering detector (ELSD) technique was utilized to develop an accurate and robust assay for the simultaneous quantification of HPMC and DM in a nanosuspension formulation. The statistical design of experiments was used to determine the influence of critical ELSD variables including temperature, pressure, and gain on accuracy, precision, and sensitivity of the assay. A robust design space was identified where it was determined that an increase in the temperature of the drift tube and gain of the instrument increased the accuracy and precision of the assay and a decrease in the nebulizer pressure value increased the sensitivity of the assay. In the optimized design space, response data showed that the assay could quantify HPMC and DM simultaneously with good accuracy, precision, and reproducibility. Overall, SEC-ELSD proved to be a powerful technique for the simultaneous quantification of HPMC and DM. This technique can be used to quantify the amount of HPMC and DM in nanosuspensions, which is critical to understanding their effects on the physical stability of nanosuspensions.

Twin screw wet granulation: Effect of process and formulation variables on powder caking during production

This work focuses on monitoring the behaviour and the mass of the built up/caking of powder during wet granulation using Twin Screw Granulator (TSG). The variables changed during this work are; powder (α-lactose monohydrate and microcrystalline cellulose (MCC)), the screw configuration (conveying and kneading elements) and the weight percentage of hydroxypropyl-methyl cellulose (HPMC) dissolved in the granulation liquid (i.e. changing liquid viscosity). Additionally, the effect of these variables on the size distribution, of the granules produced, was determined. The experiments were conducted using an acrylic transparent barrel. A stainless steel barrel was then used to conduct the two extreme granulation liquid viscosities with two different screw configurations, using lactose only. This was done to compare the findings to those obtained from the transparent barrel for validation purpose.These variables showed to affect the behaviour and the mass of the powder caking as well as the size distribution of granules. Overall, the use of kneading element resulted in uniform behaviour in caking with higher mass. Furthermore, increasing the amount of HPMC resulted in a reduction of the mass of powder caking for lactose, while showing inconsistent trend for MCC. Furthermore, lactose showed to have a greater tendency to cake in comparison to MCC.The results, for lactose, obtained from the stainless steel barrel compared well with their corresponding conditions from the transparent barrel, as the screw configuration and HPMC mass varied.

Zero‐order release three‐layered tablet with an acemetacin solid dispersion core and a hydroxypropyl methylcellulose capped matrix

ABSTRACTThe purpose of this study was to prepare a three‐layered tablet with hydroxypropyl methylcellulose (HPMC) polymers as a capped matrix to achieve a zero‐order release for acemetacin. As the middle active core, a solid dispersion in poly(vinyl pyrrolidone)–K30 polymers was manufactured via a solvent method to improve the solubility of acemetacin. A Box–Behnken design was used to optimize the formula, when the amounts of HPMC in the middle layer, HPMC in the external layer, and mannitol in the middle layer were chosen as the influencing factors. The dissolution profiles of the optimized formula exhibited superior fitting to the zero‐order release in 24 h. A bioavailability experiment was carried out by the administration of those three‐layered tablets to rabbits and their comparison with market Gaoshunsong controlled release capsules. The delayed time to reach the maximum plasma concentration, decreased the maximum plasma concentration, area under the plasma concentration‐time curve (0–48 h) AUC0–48, and area under the plasma concentration‐time curve (0–∞) AUC0–∞ were 9.33 ± 2.51 h, 8.59 ± 0.94 µg/mL, 200.81 ± 11.36 µg h/mL, and 212.902 ± 31.66 µg h/mL, respectively. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42059.

Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

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.

Hydroxypropyl Methylcellulose Reduces Particle Adhesion and Improves Recovery of Herbal Extracts During Spray Drying of Chinese Herbal Medicines

The effectiveness of hydroxypropyl methylcellulose (HPMC) as an anti-adherent during spray drying of traditional Chinese herbal extracts was explored. A small amount of HPMC (minimum concentration 8%) was sufficient to overcome problematic particle adhesion, whereas a large amount of maltodextrin (50%) was required for the same effect. HPMC exerted a strong anti-adhesive effect that was independent of the type of HPMC, raw materials used, and the process used to synthesize HPMC. The anti-adhesion mechanism was studied through an analysis of the surface tension of the prepared solutions before spray drying, the glass transition temperature (T g ), and X-ray photoelectron spectroscopy (XPS) of spray-dried powders. The T g of powders containing more than 8% HPMC was approximately 40°C and did not increase linearly with the HPMC concentration. The surface tension of Crataegi fructus extract was 54.1 ± 0.2 mN/m and further decreased to 46.6 ± 0.2 mN/m upon addition of HPMC to 24%. When the concentration of HPMC increased to 8%, potassium could not be detected on the surface of dried powders by XPS. These results suggest that modification of the surface properties of sprayed droplets/particles by HPMC increased the HPMC surface coverage of the particles and reduced adhesion during spray drying.

Pharmacokinetics and analgesic effect of ketorolac floating delivery system

Objectives: The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form.Methods: KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay.Results: The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets.Conclusion: KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.

Statistical optimization and characterization of pH-independent extended-release drug delivery of cefpodoxime proxetil using Box–Behnken design

The aim of this study was to develop and optimize the pH-independent extended-release (ER) formulations of cefpodoxime proxetil (CP) using response surface methodology by employing a 3-factor, 3-level Box–Behnken statistical design. The independent variables studied were the amount of hydroxypropyl methylcellulose (HPMC K4M), sodium alginate (SA) and microcrystalline cellulose (MCC). The drug release percent at 2, 4, 8, 14 and 24h were the target responses and were restricted to 15–30, 35–55, 55–75, 75–90 and 90–110%, respectively. The response surface methodology and multiple response optimizations utilizing a polynomial equation were used to search for the optimal formulation with a specific release rate at different time intervals. The results showed that the effect of combination of HPMC K4M and SA was the most influencing factor on the drug release from ER matrix tablets. The mechanism of drug release from ER tablets was dependent on the added amount of SA. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 25% HPMC, 15.14% SA, and 20.14% MCC was prepared according to the software determined levels. DSC and FTIR studies combined with the stability study of the optimized formulation proved the integrity of the developed formulation. The Box–Behnken experimental design facilitated the formulation and optimization of extended release hydrophilic matrix systems of CP in a short period of time and with the fewest number of experiments.

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole

Context: Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets.Objective: The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery.Materials and methods: Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release.Results: The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%.Conclusions: The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

Production of dosage forms for oral drug delivery by laminar extrusion of wet masses

Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery. Extrusion was carried out with a ram extruder. Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water. Extrudates were characterized for their tensile strength, Young’s modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO). Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3.3–4.5% w/w dry weight). Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects. For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly. For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release. This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.

Characterization during storage and dissolution of solid dispersions containing furosemide and hydroxypropyl methylcellulose

Solid dispersions containing furosemide and various amounts of hydroxypropyl methylcellulose (HPMC) were prepared by spray drying to investigate if the physical stability of amorphous furosemide during storage and dissolution could be improved by formulating the drug as a solid dispersion. All solid dispersions, containing 20, 50, or 80 w/w % HPMC, were stable for 730 days when stored at 22 °C and 33 % relative humidity (RH), whereas under accelerated storage conditions of 40 °C and 75 % RH the amorphous furosemide in the solid dispersions with 20 and 50 % HPMC converted to a crystalline form within 30 days of storage. In contrast, furosemide in solid dispersions containing 80 % HPMC stayed amorphous for 30 days. Dissolution experiments in conjunction with XRPD and in-line Raman spectroscopy showed that the addition of 80 % HPMC was necessary for complete avoidance of solid state conversion of amorphous furosemide to a crystalline form during dissolution.

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.