Hydroxypropyl Methylcellulose Tablets Research Articles

Development of Sustained Release System Based on High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose Sodium as a Gel Former.

Croscarmellose sodium, generally used as a superdisintegrant in pharmaceutical formulations, is hydrolyzed to form the gel structure under basic pH conditions. Utilizing this property of croscarmellose sodium, we developed a novel sustained release (SR) system. Immediate release (IR) and SR tablets containing croscarmellose sodium, alkaline excipients and/or hydroxypropyl methylcellulose (HPMC) were prepared and examined for wet strength and in vitro drug release behavior. In vivo oral drug absorption was evaluated for IR tablets, HPMC tablets and our novel SR tablets in fasted Beagle dogs. To form the gel structure even under the physiological condition, alkaline excipients were added into the formulation containing croscarmellose sodium. Furthermore, HPMC was used to make the gel structure strong enough against mechanical destructive forces. The novel alkalized croscarmellose sodium-HPMC (ACSH) SR tablet, consisting of croscarmellose sodium, alkaline excipients, and HPMC, successfully sustained the release of acetaminophen, ibuprofen, or nicardipine hydrochloride, compared with the IR tablets. The ACSH SR system provided a better release of acetaminophen than the HPMC tablet without croscarmellose sodium in the release study using a small volume of liquid, suggesting that substantial release and subsequent absorption would be expected in the distal intestinal segments after oral dosing. The in vivo oral absorption study revealed that the ACSH SR system successfully suppressed and prolonged the plasma concentrations of acetaminophen. This novel ACSH SR system prepared with croscarmellose sodium, alkaline excipients, and HPMC, would be a promising SR formulation for enabling substantial drug absorption in the distal intestinal segments.

Evaluation of Modified Date Palm (Phoenix dactylifera L.) Mucilage as a Potential Pharmaceutical Excipient

Investigation on natural sources from plants, animals, and microorganisms that produce gums and mucilages goes on increasing day by day to check their pharmaceutical applications. Different mucilages have been studied for their pharmaceutical effects but the use of date palm (Phoenix dactylifera L.) mucilage as a pharmaceutical excipient is still under the cover. The aim of this study was therefore to evaluate and compare the flow property and binding ability of crude, purified, modified (hydrolyzed and grafted), green synthesized nanoparticles (Zinc oxide (ZnO), cuperic oxide (CuO), silver (Ag), and gold (Au)) of date palm mucilage with hydroxy propyl methyl cellulose (HPMC) and commercially available paracetamol tablets. Previously purified mucilage (with 58.4% yield) was subjected to modification (i.e., acidic, basic, and enzymatic), grafting (polyacrylamide), and green synthesis of nanoparticles. Flow properties of powdered (granular) crude, purified, modified, and nanoparticles were studied and compared with flow properties of HPMC and paracetamol tablet granules. Tablets were made using granules of all types of date palm mucilage (discussed above), HPMC, and granules of paracetamol tablets to study and compare weight uniformity, hardness, friability, dissolution rate, and disintegration time. When 100 mg/kg of mucilage sample was given to mice no oral toxicity was found. The results obtained during this study were within the acceptable ranges given in pharmacopeias. The pseudoplastic flow behavior, hygroscopic nature, increased solubility, and swelling index across the increase in temperature, hardness of the tablets, friability, and drug release behavior were found better than HPMC and the binders used in commercially available paracetamol, hence making the date palm mucilage (crude, purified, and modified) an excellent excipient to be used in pharmaceutical dosage forms.

Thai glutinous rice starch modified by ball milling and its application as a mucoadhesive polymer

This study aimed to investigate physicochemical properties and potential application as a mucoadhesive polymer of Thai glutinous rice starch modified by planetary ball milling. XRD and ATR-FTIR results indicated a reduction in crystallinity of starch after ball milling. Different ball milling times, ranging from 5 to 45 min, resulted in modified glutinous rice starch (MGRS) with different levels of crystallinity loss, and therefore varying degrees of cold water solubility, swelling capacity, and gelatinized dispersion viscosity. Investigation of mucoadhesive properties using Texture Analyzer with porcine mucosa demonstrated that MGRS tablets exhibited greater mucoadhesive abilities compared to hydroxypropyl methylcellulose tablets, but weaker than those of sodium carboxymethylcellulose tablets. Tablets made of 15-min-milled MGRS had comparable tableting, swelling and mucoadhesiveness, but lower erosion compared to 45-min-milled MGRS. Conclusively, ball milling treatment could successfully induce the mucoadhesive properties of Thai glutinous rice starch and expand its application as mucoadhesive polymer.

Swelling of Zein Matrix Tablets Benchmarked against HPMC and Ethylcellulose: Challenging the Matrix Performance by the Addition of Co-Excipients.

Zein is an insoluble, yet swellable, biopolymer that has been extensively studied for its applications in drug delivery. Here, we screened the effect of co-excipients on the swelling and drug release of zein tablets. All throughout the study the behavior of zein was benchmarked against that of hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC). Tablets containing either zein, HPMC, or EC alone or in combination with co-excipients, namely lactose, dicalcium phosphate (DCP), microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), or sodium lauryl sulfate (SLS) were prepared by direct compression. Matrix swelling was studied by taking continuous pictures of the tablets over 20 h, using a USB microscope connected to a PC. The overall size change and the axial and radial expansion of the tablets were automatically extrapolated from the pictures by image analysis. Moreover, drug release from tablets containing ternary mixtures of zein, co-excipients and 10% propranolol HCl was also studied. Results showed that zein matrices swelled rapidly at first, but then a plateau was reached, resulting in an initial rapid drug burst followed by slow drug release. HPMC tablets swelled to a greater extent and more gradually, providing a more constant drug release rate. EC did not practically swell, giving a nearly constant drug release pattern. Among the additives studied, only MCC increased the swelling of zein up to nearly three-fold, and thus suppressed drug burst from zein matrices and provided a nearly constant drug release over the test duration. Overall, the incorporation of co-excipients influenced the swelling behavior of zein to a greater extent compared to that of HPMC and EC, indicating that the molecular interactions of zein and additives are clearly more complex and distinct.

Optimization of piribedil mucoadhesive tablets for efficient therapy of Parkinson’s disease: physical characterization and ex vivo drug permeation through buccal mucosa

Objective: The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson’s disease.Methods: Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa.Results: Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6 h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets.Conclusion: Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson’s disease.

에틸렌 발생 tablet 제조 및 활성 최적 조건 구명

Ethylene (C2H4) is a naturally occurring hormone in some fruit. This study was carried out to manufactureethylene-producing tablets. The Ethylene-producing tablets were manufactured from ethephon and excipient mixtures, including Prosolv, Hydroxypropylmethylcellulose (HPMC) and Crosscamellose. Ethylene production increased with the increases in temperature. In the aspect of pH condition, ethylene productions at pH 7.0 and pH 9.0 were less than 2 ppm. On the other hand, at pH 13.0, ethylene production from the Prosolv, HPMC, and Crosscamellose tablets was 94.05, 126.28, and 100.11 ppm, respectively. The friability of the Prosolv and HPMC tablets were 0.1 and 0.3%, respectively, while the Crosscamellose tablet was 54.1%. indicating that the Crosscarmellose tablet was not appropriate as an ethylene production tablet. In addition, there were huge variations in disintegration times; the Prosolv, Crosscamelose, and HPMC tablets took 1, 5 min, and 7 min more than respectively. Ethylene production was gradually increased up to 20 hr for the Prosolv tablet and then remained stable

Diffusion and Swelling Measurements in Pharmaceutical Powder Compacts Using Terahertz Pulsed Imaging

Tablet dissolution is strongly affected by swelling and solvent penetration into its matrix. A terahertz-pulsed imaging (TPI) technique, in reflection mode, is introduced as a new tool to measure one-dimensional swelling and solvent ingress in flat-faced pharmaceutical compacts exposed to dissolution medium from one face of the tablet. The technique was demonstrated on three tableting excipients: hydroxypropylmethyl cellulose (HPMC), Eudragit RSPO, and lactose. Upon contact with water, HPMC initially shrinks to up to 13% of its original thickness before undergoing expansion. HPMC and lactose were shown to expand to up to 20% and 47% of their original size in 24 h and 13 min, respectively, whereas Eudragit does not undergo dimensional change. The TPI technique was used to measure the ingress of water into HPMC tablets over a period of 24 h and it was observed that water penetrates into the tablet by anomalous diffusion. X-ray microtomography was used to measure tablet porosity alongside helium pycnometry and was linked to the results obtained by TPI. Our results highlight a new application area of TPI in the pharmaceutical sciences that could be of interest in the development and quality testing of advanced drug delivery systems as well as immediate release formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:1658–1667, 2015

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).

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.

Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes

The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH6) and acidic (pH2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (Ea) values calculated from caffeine diffusivities were in the range of Fickian transport (20–40kJmol−1). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer–Peppas model would indicate anomalous transport. However, the low apparent Ea values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent Ea values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true Ea would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion–erosion mechanism, both at pH6 and 2.

Evaluation of hydrophilic, hydrophobic and waxy matrix excipients for sustained release tablets of Venlafaxine hydrochloride

Objective: Venlafaxine is freely soluble In water and administered orally as hydrochloride salt In two to three divided doses. In the present investigation different release retarding matrices have been evaluated for sustained release of venlafaxine hydrochloride (VH) from the formulated tablets.Materials and methods: Sustained release matrix tablets were formulated using different hydrophilic, hydrophobic and waxy materials as matrix formers. Tableting was done by pre-compression, direct compression and hot melt granulation depending on the type of matrix material used and evaluated for different tests. The formulated tablets were compared with commercial venlafaxine products. In vitro drug dissolution profiles were fitted In different mathematical models to elucidate the release mechanism.Results: Dissolution data showed that commercial formulations Venlor XR® and Venfax PR® released the entire drug withIn 8 h where as the formulated tablets with hydroxypropylmethylcellulose (HPMC) and cetyl alcohol as matrix formers provided sustained release of drug for 14–15 h. The release was found to follow Hixson Crowel and Higuchi kinetics for HPMC and cetyl alcohol tablets, respectively.Conclusion: The developed matrix tablet formulations with HPMC and cetyl alcohol provided sustained release profiles for prolonged periods than commercial formulations.

Influence of pH Modifiers and HPMC Viscosity Grades on Nicotine–Magnesium Aluminum Silicate Complex-Loaded Buccal Matrix Tablets

Hydroxypropyl methylcellulose (HPMC) tablets containing nicotine-magnesium aluminum silicate (NCT-MAS) complex particles and pH modifiers, namely, sodium chloride, citric acid, and magnesium hydroxide, were prepared using the direct compression method. The effects of HPMC viscosity grades and pH modifiers on NCT release and permeation of the matrix tablets were examined. The results showed that the higher the viscosity grade of HPMC that was used in the tablets, the lower was the unidirectional NCT release rate found. The unidirectional NCT permeation was not affected by the viscosity grade of HPMC because the NCT diffusion through the mucosal membrane was the rate-limiting step of the permeation. Incorporation of magnesium hydroxide could retard NCT release, whereas the enhancement of unidirectional NCT release was found in the tablets containing citric acid. Citric acid could inhibit NCT permeation due to the formation of protonated NCT in the swollen tablets at an acidic pH. Conversely, the NCT permeation rate increased with the use of magnesium hydroxide as a result of the neutral NCT that formed at a basic microenvironmental pH. The swollen HPMC tablets, with or without pH modifiers, gave sufficient adhesion to the mucosal membrane. Furthermore, the addition of magnesium hydroxide to the matrix tablets was the major factor in controlling buccal delivery of NCT. This study suggests that the NCT-MAS complex-loaded HPMC tablets, which contained magnesium hydroxide, are potential buccal delivery systems of NCT.

Use of propranolol-magnesium aluminium silicate intercalated complexes as drug reservoirs in polymeric matrix tablets

The objective of the present study was to investigate the use of propranolol–magnesium aluminium silicate intercalated complexes as drug reservoirs in hydroxypropylmethylcellulose tablets. The matrix tablets containing the complexes were prepared and characterised with respect to propranolol release and were subsequently compared with those loading propranolol or a propranolol–magnesium aluminium silicate physical mixture. Additionally, the effects of varying viscosity grades of hydroxypropyl methylcellulose, compression pressures and calcium acetate incorporation on the drug release characteristics of the complex-loaded tablets were also examined. The results showed that the complex-loaded tablets have higher tablet hardness than those containing propranolol or a physical mixture. The drug release from the complex-loaded tablets followed a zero-order release kinetic, whereas an anomalous transport was found in the propranolol or physical mixture tablets. The drug release rate of the complex tablet significantly decreased with increasing hydroxypropylmethylcellulose viscosity grade. Increase in the compression pressure caused a decrease in the drug release rate of the tablets. Furthermore, the incorporation of calcium ions could accelerate propranolol release, particularly in acidic medium, because calcium ions could be exchanged with propranolol molecules intercalated in the silicate layers of magnesium aluminium silicate. These findings suggest that propranolol-magnesium aluminium silicate intercalated complexes show strong potential for use as drug reservoirs in matrix tablets intended for modifying drug release.

Modelling of pharmaceutical tablet swelling and dissolution using discrete element method

This work presents a novel use of the Discrete Element Method (DEM) combined with inter-particle mass transfer in order to simulate polymer swelling and dissolution. Each particle can absorb water and swell, pushing on its neighbours and causing an overall expansion. Once the disentanglement threshold is reached, the polymer dissolves and the particle reduces in size. This paper applies DEM to simulate the radial swelling and dissolution of cylindrical tablets. The method was validated against exact numerical solution of the same system to assess the accuracy of the DEM simulations for different DEM particle sizes. Parametric studies were done to assess the impact of physical parameters – namely the concentration-dependent diffusion coefficient of water through the polymer, the dissolution rate constant of the polymer and the disentanglement threshold of the polymer – on the radial expansion of the tablet. It was found that different settings of the concentration-dependent water diffusion coefficient function could produce similar radial expansion curves but with different internal concentration profiles. Increasing the dissolution rate constant or decreasing the disentanglement threshold of the polymer caused a reduction in the maximum radius of tablet. Lastly, ATR-FTIR spectroscopic imaging was used to obtain chemical images of a pure hydroxy-propyl methylcellulose (HPMC) tablet swelling and dissolving. The model was optimised to match both the HPMC tablet radius and the concentration profiles over time.

Sol-Gel Behavior of Hydroxypropyl Methylcellulose (HPMC) in Ionic Media Including Drug Release.

Sol-gel transformations in HPMC (hydroxypropyl methylcellulose) are being increasingly studied because of their role in bio-related applications. The thermo-reversible behavior of HPMC is particularly affected by its properties and concentration in solvent media, nature of additives, and the thermal environment it is exposed to. This article contains investigations on the effects of salt additives in Hofmeister series on the HPMC gelation. Various findings regarding gelation with salt ions as well as with the ionic and non-ionic surfactants are presented. The gel formation in physiological salt fluids such as simulated gastric and intestine fluids is also examined with the interest in oral drug delivery systems. The processes of swelling, dissolution and dispersion of HPMC tablets in simulated bio-fluids are explored and the release of a drug from the tablet affected by such processes is studied. Explanations are provided based on the chemical structure and the molecular binding/association of HPMC in a media. The test results at the body or near-body temperature conditions helped in understanding the progress of the gelation process within the human body environment. The detailed interpretation of various molecule level interactions unfolded the sol-gel mechanisms and the influence of a few other factors. The obtained test data and the established mathematical models are expected to serve as a guide in customizing applications of HPMC hydrogels.

Drug diffusion from polymeric delivery devices: a problem with two moving boundaries

An existing model for solvent penetration and drug release from a spherically shaped polymeric drug delivery device is revisited. The model has two moving boundaries, one that describes the interface between the glassy and rubbery states of the polymer, and another that defines the interface between the polymer ball and the pool of solvent. The model is extended so that the nonlinear diffusion coefficient of drug explicitly depends on the concentration of solvent, and the resulting equations are solved numerically using a front fixing transformation together with a finite difference spatial discretisation and the method of lines. We present evidence that our scheme is much more accurate than a previous scheme. Asymptotic results in the small time limit are presented, which show how the use of a kinetic law as a boundary condition on the innermost moving boundary dictates qualitative behaviour, the scalings being very different to the similar moving boundary problem that arises from modelling the melting of an ice ball. The implication is that the model considered here exhibits what is referred to as non-Fickian or Case~II diffusion which, together with the initially constant rate of drug release, has certain appeal from a pharmaceutical perspective. References G. Astarita and G. C. Sarti. A class of mathematical models for sorption of swelling solvents in glassy polymers. Polymer Engineering and Science., 18, 1978, 388--395. doi:10.1002/pen.760180510. D. S. Cohen and T. Erneux. Free boundary problems in controlled release pharmaceuticals. I: Diffusion in glassy polymers. SIAM Journal on Applied Mathematics., 48, 1988, 1451--1465. http://www.jstor.org/stable/2101759. D. S. Cohen and T. Erneux.. Free boundary problems in controlled release pharmaceuticals. II: Swelling-controlled release. SIAM Journal on Applied Mathematics., 48, 1988, 1466--1474. http://www.jstor.org/stable/2101760. T. Higuchi. Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. Journal of Pharmaceutical Sciences., 52, 1963, 1145--1149. doi:10.1002/jps.2600521210. J.-S. Lin, C.-C. Hwang, C.-M. Lin, and J.-Y. Lai. Solvent transport in spherical polymer-penetrant systems. Chemical Engineering Science., 56, 2001, 151--156. doi:10.1016/S0009-2509(00)00410-3. J.-S. Lin and Y.-L. Peng. Swelling controlled release of drug in spherical polymer-penetrant systems. International Journal of Heat and Mass Transfer., 48, 2005, 1186--1194. doi:10.1016/j.ijheatmasstransfer.2004.08.031. S. W. McCue, M. Hsieh, T. J. Moroney, and M. I. Nelson. Asymptotic and numerical results for a model of solvent-dependent drug diffusion through polymeric spheres. Submitted. B. Narasimhan and N. A. Peppas. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier. Journal of Pharmaceutical Sciences., 86, 1997, 297--304. doi:10.1021/js960372z. F. A. Radu, M. Bause, P. Knabner, G. W. Lee, and W. C. Friess. Modeling of drug release from collagen matrices. Journal of Pharmaceutical Sciences, 91, 2002, 964--972. doi:10.1002/jps.10098. J. Siepmann, K. Podual, M. Sriwongjanya, N. A. Peppas and R. Bodmeier. A new model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets. Journal of Pharmaceutical Sciences., 88, 1999, 65--72. doi:10.1021/js9802291. S. Kill and K. Dam-Johansen. Controlled drug delivery from swellable hydroxypropylmethylcellulose matrices: model-based analysis of observed radial front movements. Journal of Controlled Release., 90, 2003, 1--21. doi:10.1016/S0168-3659(03)00122-6. N. Wu, L.-S. Wang, D. C.-W. Tan, S. M. Moochhala, and Y.-Y. Yang. Mathematical modeling and in vitro study of controlled drug release via a highly swellable and dissoluble polymer matrix: polyethylene oxide with high molecular weights. Journal of Controlled Release., 102, 2005, 569--581. doi:10.1016/j.jconrel.2004.11.002.

Effect of source variation on drug release from HPMC tablets: Linear regression modeling for prediction of drug release

The aim of this study was to investigate the effect of source variation of hydroxypropyl methylcellulose (HPMC) raw material on prediction of drug release from HPMC matrix tablets. To achieve this objective, the flow ability (i.e., angle of repose and Carr's compressibility index) and apparent viscosity of HPMC from 3 sources was investigated to differentiate HPMC source variation. The physicochemical properties of drug and manufacturing process were also incorporated to develop the linear regression model for prediction of drug release. Specifically, the in vitro release of 18 formulations was determined according to a 2 × 3 × 3 full factorial design. Further regression analysis provided a quantitative relationship between the response and the studied independent variables. It was found that either apparent viscosity or Carr's compressibility index of HPMC powders combining with solubility and molecular weight of drug had significant impact on the release behavior of drug. The increased drug release was observed when a greater in drug solubility and a decrease in the molecular weight of drug were applied. Most importantly, this study has shown that the HPMC having low viscosity or high compressibility index resulted in an increase of drug release, especially in the case of poorly soluble drugs.

Effect of FITC-dextran molecular weight on its release from floating cetyl alcohol and HPMC tablets

The release mechanism of high molecular weight fluorescein isothiocyanate dextrans (FITC-dextrans) from HPMC hydrogel matrices was studied. An anomaly was noted in the release behaviour of a series of high molecular weight FITC-dextrans from a tablet formulation designed to float in stomach contents. The tablets contained sodium bicarbonate and hydroxypropylmethyl cellulose (HPMC) in a cetyl alcohol matrix. When hydrated in an acid medium, this tablet consisted of a mixed solid with a viscous surface layer containing carbon dioxide bubbles through which the active ingredient (FITC-dextran) was released into the aqueous environment. However, it was observed that, above a critical molecular weight (approx. 65 kDa), the FITC-dextran was only released into the medium by an erosion-type mechanism, whereas, below this value, both diffusion and erosion processes took place. The key constraint appeared to be the apparent gel pore-size of the hydrated HPMC that was approximately 12 nm in diameter, irrespective of the molecular weight of the HPMC samples evaluated. It was concluded that FITC-dextran release was controlled by both FITC-dextran molecular weight and the HPMC hydrogel structure.

Development of Prolonged Action, Bioadhesive and Slowly Dissolving Minitablets

Minitablets can be used either single or multiple unit sustained release dosage form. The objectives of this study were to prepare and evaluate the prolonged action, bioadhesive and slowly dissolving minitablets. The minitablets (Ø 2.5 mm, 7 mg) were prepared by direct compression method using 75%w/w of various hydrophilic polymers: hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), carboxy methylcellulose (CMC), pectin (PT) and chitosan (CS). Spray dried lactose was used as diluent. Prior to compression, the angle of repose, bulk-tab density and %compressibility of each mixed powder were evaluated. The rate of hydration and erosion of the obtained minitablets were carried out in phosphate buffer (pH 7.4). The powder blends containing HPC, CMC or HPMC showed satisfactory flow properties and compressibility. Accordingly, the prepared matrix tablets of HPC, CMC and HPMC showed good physical properties such as hardness, while those of CS and PT showed poor properties. The degree of swelling were ranked as CS>CMC>PT>HPC>HPMC, while the erosion were ranked as CMC≈HPMC≈PT > HPC≈CS. Adhesion time of these minitablets on isolated pig intestine was >30 min for CMC, PT and CS tablets while HPC and HPMC tablets exhibited weaker bioadhesion. In conclusion, among tested polymers, CS, PT and CMC were appropriate for prolonged action, bioadhesive and slowly dissolving minitablets.

Influence of soluble and insoluble cyclodextrin polymers on drug release from hydroxypropyl methylcellulose tablets

Background: The influence of β-cyclodextrin (β-CD) polymers on drug release from hydroxypropyl methylcellulose (HPMC) matrices has not been reported in the literature. Aim: The influence of monomeric β-CD and both soluble and insoluble β‐CD polymers on drug release from tablets containing either 30% or 50% hydroxypropyl methylcellulose has been studied using diflunisal (DF) as model drug. Method: The DF-β-CD inclusion complex (1:1 M) was prepared by coevaporation and characterised using X-ray diffraction, differential thermal analysis, and IR spectroscopy. The dissolution assays were performed according to the USP paddle method. Results: The incorporation of β-CD in the complexed form increases drug release from hydroxypropyl methylcellulose tablets in comparison with the physical mixture because of the better solubilization of the drug. The soluble polymer promotes drug release to a higher extent than the physical mixture with monomeric β-CD, but the insoluble polymer, which is itself a hydrogel, gives rise to the most retarded release profile, probably by retention of the drug in its structure. The formulations containing physical mixtures with either β‐CD or the soluble polymer present an optimum adjustment to zero-order release kinetics, and the inclusion complex followed non-Fickian diffusion according to the Korsmeyer–Peppas model. Conclusion: The release profile of DF from a HPMC matrix can be modulated in different ways by the use of either monomeric or polymeric β-CD.