Controlled-Release Tablet Matrices from Carrageenans: Compression and Dissolution Studies

ABSTRACT

This study investigates the potential of two commercial carrageenans, Gelcarin GP-379® (i-carra-geenan) and Viscarin GP-209® (X-carrageenan) to be used for the preparation of controlled-release tablet matrices. Tablets were compressed on an instrumented Stokes single punch machine and compression characteristics of the carrageenans were analyzed. Heckel plots using out-of-die tablet densities were linear with calculated yield pressures of 81.3 MPa and 105.2 MPafor i- and X-carrageenan, respectively. Drug release from tablet formulations that contained equal amounts of the two carrageenans had near zero-order release profiles. There was little or no effect of tablet compression pressure on the drug release profiles from 70 to 175 MPa. As drug loading was increased from 5 to 20%, the diffusional exponent decreased from 1.056 to 0.678. Thirty percent drug loading resulted in breakup of tablets during dissolution and departure from zero-order release. Multiple regression analysis was used to predict the time for 50% release as a function of the concentration of the two carrageenans and a third filler material, microcrystalline cellulose. Predicted values were in good agreement with observed values and R² for the final cubic model was 0.9984.     

Sustained release of acetaminophen from a heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers

This study examined the release of acetaminophen (APAP) from hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) matrices. The effect of pseudoephedrine (PE) as a co-active, HPMC:HPC ratio, polymer loading, pH of the dissolution media, and compression force on APAP release were studied. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and HPC were compressed into tablets at different compression forces. APAP release from the matrix tablets was not considerably influenced by changes in HPMC:HPC ratio or compression force. The rate of drug release was significantly affected by pH of the dissolution media, total polymer loading, and the presence of PE. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP. Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45. Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.4. The drug release data showed a good fit to the Power Law Model. The mechanism of drug release is consistent with a complex behavior. The results of the tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation mechanism.     

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

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

Potential of carrageenans to protect drugs from polymorphic transformation.

Carrageenans were analysed in mixture with polymorphic drugs to test their potential for minimising polymorphic or pseudopolymorphic transitions, which are induced by the tableting process. The kappa-carrageenans Gelcarin GP-812 NF and Gelcarin GP-911 NF and the iota-carrageenan Gelcarin GP-379 NF were tested in comparison to the well-known tableting excipients microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), and dicalcium phosphate dihydrate (DCPD). Amorphous indomethacin was chosen as model drug since its well-known recrystallisation behaviour can be mechanically stimulated. Further on, theophylline monohydrate was used. Its dehydration is induced by tableting. Pure materials and mixtures containing 20% (w/w) drug were compressed up to different maximum relative densities. The data obtained during tableting were analysed by three-dimensional (3D) modelling. Afterwards tablets were broken and examined by Fourier transform Raman spectroscopy in order to determine the degree of transformation inside the tablet. For quantitative interpretation, the intensities of representative bands were used. Thermal analysis was used additionally. Using 3D modelling a decrease of plastic deformation can be noticed in the order HPMC>MCC>carrageenans, whereas DCPD represents an exception because of brittle fracture. Best hindrance of polymorphic transformation showed the carrageenans, the hindrance was slightly worse for HPMC. MCC and DCPD could not hinder transformation. A complete protection of the amorphous form could not be achieved. For theophylline monohydrate, the results were similar.     

Oral controlled release formulations of rifampicin. Part II: Effect of formulation variables and process parameters on in vitro release

Hydrophilic controlled release matrix tablets of rifampicin, a poorly soluble drug, have been formulated using hydroxypropyl methylcellulose (HPMC) polymer (low, medium, and high viscosity) by direct compression method. Influence of formulation variables and process parameters such as drug:HPMC ratio, viscosity grade of HPMC, drug particle size, and compression force on the formulation characters and drug release has been studied. Our results indicated that the release rate of the drug and the mechanism of release from the HPMC matrices are mainly controlled by the drug:HPMC ratio and viscosity grade of the HPMC. In general, decrease in the drug particle size decreased the drug release. Lower viscosity HPMC polymer was found to be more sensitive to the effect of compression force than the higher viscosity. The formulations were found to be stable and reproducible.     

Amphiphilic association of ibuprofen and two nonionic cellulose derivatives in aqueous solution

The aqueous interaction of the sodium salt of ibuprofen with the cellulose ethers ethyl hydroxyethyl cellulose, EHEC, and hydroxypropyl methyl cellulose, HPMC, has been investigated in the concentration range 0-500 mM ibuprofen and 0.1-1% (w/w) polymer, by cloud point, capillary viscometry, equilibrium dialysis, and fluorescence probe techniques. Ibuprofen forms micelles in pure water, with the critical micelle concentration, cmc, at 180 mM. A combination of time-resolved and static fluorescence quenching shows that micelle-like ibuprofen aggregates are formed in the solution. The average aggregation number of pure ibuprofen micelles in water is about 40. In the presence of EHEC or HPMC the aggregation numbers decrease. The interaction of ibuprofen with cellulose ethers is similar to the normally accepted model for polymer-surfactant interaction, although more complex. Ibuprofen adsorbs to the polymer in the form of mixed polymer-drug micelles, noncooperatively up to cmc and cooperatively when cmc is passed. The interaction starts below 50 mM ibuprofen as monitored by the fluorescent probes pyrene and 1,3-di(1-pyrenyl)propane, P3P, with a maximum in microviscosity below cmc, corresponding to polymer-dense mixed micelles. The study illustrates the importance of a precise apprehension of the aggregation behavior as a background for transport studies in drug-polymer systems.     

Bioavailability of ibuprofen from hot-melt extruded mini-matrices

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.     

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets

The objective of this study was to evaluate the potential of Carbopol^® 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC^® K15M) and Eudragit^® L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P?<?0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P?<?0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P?<?0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P?<?0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P?<?0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.     

Characterization of cellulosic hot-melt extruded films containing lidocaine.

Hot-melt extrusion technology was used to produce thin films containing a model drug, lidocaine, and the cellulosic polymers hydroxypropyl cellulose (HPC) and hydroxypropyl methyl cellulose (HPMC). Two film formulations were extruded and compared, one containing only HPC and the other containing HPC:HPMC (80:20). Thermal analysis of the films using differential scanning calorimetry (DSC) suggested that the drug existed in the amorphous condition, which was confirmed by wide angle X-ray diffractometry. Sustained release of the drug was observed from both of the polymer matrices. Dissolution profiles suggested that HPMC retarded the drug release from HPC:HPMC (80:20) films. However, the mechanism of drug release from both of the films was predominantly diffusion of the drug through the polymer matrices. Incorporation of HPMC also increased both adhesive strength and work of adhesion as compared to the HPC-only films.     

The influence of drugs on the properties of gels and swelling characteristics of matrices containing methylcellulose or hydroxypropylmethylcellulose

The cloud points, matrix swelling and gel layer formation in matrices containing cellulose ethers and indomethacin, propranolol hydrochloride or tetracycline hydrochloride have been investigated. The two hydrochloride salts contributed to the matrix swelling and gel layer formation, maintaining the integrity of matrices containing methylcellulose. Gel layer formation, measured by thermomechanical analysis was most rapid, and the layer thickest, in matrices containing propranolol hydrochloride. This mimicked cloud point determination where propranolol salted the cellulose ethers into solution to a greater extent than tetracycline. The poorly soluble indomethacin failed to contribute to swelling and gel layer formation. Studies, using U-tube viscometry, indicated that the viscosity of gels containing HPMC E4M, HPMC F4M, HPMC K4M and methylcellulose reduced on storage. This appeared to be further catalysed by the inclusion of drugs, and especially of tetracycline hydrochloride in the gels.     

Effect of various surfactants and their concentration on controlled release of captopril from polymeric matrices

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC (1:1) matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.     

Formulation and in vitro evaluation of prednisolone buccoadhesive tablets

In this research, the effect of mucoadhesive polymers such as hydroxyl propyl methyl cellulose (HPMC) with viscosity grade 60 and 500 mPas, sodium carboxy methyl cellulose (NaCMC) and carbopol 934 (Cp 934) alone or in combination with each other on the release profile of prednisolone was studied and mucoadhesion strength of these buccoadhesive formulations was evaluated. The results showed that the release of prednisolone from HPMC with viscosity grade 60 mPas and Cp 934 alone was fast and their mucoadhesion strengths was low. On the other hand, the release rates of prednisolone from the HPMC viscosity grade 500 mPas and NaCMC and mucoadhesion strengths were moderate and suitable. The results showed that with different blends of HPMC viscosity grade 500 mPas or NaCMC and Cp 934 with increasing in HPMC or NaCMC/Cp 934 ratio a remarkable decrease in the rate of drug release and an appreciable increase in the mucoadhesion strength was observed. Except from the formulations prepared with HPMC viscosity grade 60 and 500 mPas, other formulation had more fluctuations in release profiles and their kinetics of release were not fitted to zero order model.     

The effect of polymer blends on release profiles of diclofenac sodium from matrices.

The purpose of this study was to evaluate the effect of polymer blends on the in vitro release profile of diclofenac sodium. Several controlled release matrices of diclofenac sodium with different proportions of hydroxypropyl methylcellulose (HPMC; viscosity grade 60 and 500 mPa.s), carbopol 940 and lactose as a water soluble filler were prepared. The results showed that when HPMC (viscosity grade 60 mPa.s) alone was used as matrix former, diclofenac sodium was released fast but the release rate became slower with HPMC (viscosity grade 500 mPa.s) at higher polymer/drug ratios (more than 0.8:1). However in lower polymer/drug ratios (lower than 0.7:1) the release rate still was fast. The results showed that carbopol can extend the release time appreciably but the release profiles had considerable fluctuations, and drug release in first hours was slow but increased appreciably with time at the end of profiles. When an appropriate blend of HPMC (viscosity grade 60 or 500 mPa.s) and carbopol 940 was used, the drug release became more uniform and its kinetic approached to zero order and release fluctuations were diminished. The results with these polymer blends showed that it is possible to reduce the total amounts of polymer in each formulation. According to kinetic analysis data, drug release from these matrix tablets did not follow Fick's law of diffusion and the results were in agreement with the earlier reports.     

Release of theophylline and carbamazepine from matrix tablets - Consequences of HPMC chemical heterogeneity

The release of theophylline and carbamazepine from matrix tablets composed of microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) was studied. The aim was to investigate the effect of different substituent heterogeneities of HPMC on the drug release from matrix tablets composed of either 35% or 45% HPMC. The release of the poorly soluble carbamazepine was considerably affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12 h between the formulations of different HPMC batches. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. In addition, results from magnetic resonance imaging showed that the rate of water transport into the tablets was similar. This explained the comparable results of the release of the sparingly soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets were considerably different. Thus, it can be concluded that the drug release was highly affected by the substituent heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion.     

Formulation and Evaluation of Cefixime Trihydrate Matrix Tablets Using HPMC,Sodium CMC,Ethyl Cellulose

The objective of the present work is to design sustained release matrix tablets of cefixime trihydrate by incorporating drug in a matrix made up of release retardant polymers, which prolong drug release leading to minimization of the peak and valley effect in the plasma and provide patient convenience. The effect of combination of polymers on parameters like release pattern, release mechanism of the drug were studied. Total nine formulations each containing 200 mg of drug were prepared by direct compression method. The formulations F-1, F-2, F-3 were prepared with a 1:1 drug to polymer ratio using hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose. F-4 was prepared with a 1:1 ratio of hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, F-5 as prepared with a 1:1 ratio of hydroxypropyl methylcellulose and ethyl cellulose, F-6 was prepared with a 1:1 ratio of carboxymethyl cellulose sodium and ethyl cellulose, F-7, F-8, F-9 were prepared by using polymers hydroxypropyl methylcellulose, carboxymethyl cellulose sodium and ethyl cellulose in the ratios of 0.5:0.5:1, 0.5:1:0.5, and 1:0.5:0.5. Designed matrix tablets were evaluated for various pre-compression and post-compression parameters. Formulation F-5 showed 102.15 % release at the end of 12 h and it is selected as the best formulation. All Formulations followed zero order with non-Fickian diffusion method.     

Gastroretentive drug delivery systems with L-dopa based on carrageenans and hydroxypropylmethylcellulose

A comprehensive study was conducted to investigate the effects of carrageenans, and hydroxypropylmethylcellulose (HPMC) on the properties of hydrodynamically balanced systems (HBS) containing L-dopa as a model drug. The novel integrated approach included measurements of: solvent uptake, erosion, apparent density and changes in the internal structure of dosage forms during dissolution test by means of a USP4 compatible MRI. Differences in water ingress into the matrices with pure carrageenans (ι, κ, λ) or low viscous HPMC, were detected by non-invasive magnetic resonance imaging. Matrices based on carrageenans subjected to rapid hydration and erosion, were not able to maintain satisfactory floating properties for a sufficiently long period of time. The application of carrageenans in mixtures with HMC promoted water uptake by HBS formulations. The effect produced by varying the polymer blend's composition on release of the L-dopa was also studied. Dissolution data was fitted to Korsmeyer-Peppas equation. For matrices containing mixtures of carrageenan and HPMC, the linear increase in the releasing rate constant, K, with the carrageenan content in the matrix was observed.     

The influence of excipients on drug release from hydroxypropyl methylcellulose matrices

The influence of commonly used excipients, spray-dried lactose (SDL), microcrystalline cellulose (MCC), and partially pregelatinized maize starch (Starch 1500) on drug release from hydroxypropyl methylcellulose (HPMC, hypromellose) matrix system has been investigated. A model formulation contained 30%w/w drug, 20%w/w HPMC, 0.5%w/w fumed silica, 0.25%w/w magnesium stearate, and 49.25%w/w filler. Chlorpheniramine maleate and theophylline were used as freely (1 in 4) and slightly (1 in 120) water-soluble drugs, respectively. It was found that for both drugs, addition of 20 to 49.25%w/w Starch 1500 resulted in a significant reduction in drug release rates compared to when MCC or SDL was used. The study showed that using lactose or microcrystalline cellulose in the formulations resulted in faster drug release profiles. Partially pregelatinized maize starch contributed to retardation of both soluble and slightly soluble drugs. This effect may be imparted through synergistic interactions between Starch 1500 and HPMC and the filler actively forming an integral part within the HPMC gel structure.     

A novel approach to sustained pseudoephedrine release: differentially coated mini-tablets in HPMC capsules

We developed and optimized a novel pseudoephedrine hydrochloride (PSE) sustained-release dosage form. The system comprises immediate-release mini-tablets (IRMT) and sustained-release mini-tablets (SRMT) contained in a hydroxypropyl methylcellulose (HPMC) capsule. The IRMT contained PSE, excipients and low-substituted hydroxypropyl cellulose (a disintegrant), and the tablets were coated with HPMC, a water-soluble polymer. IRMT prepared with varying amounts of low-substituted hydroxypropyl cellulose all dissolved completely within the first 60min, so low-substituted hydroxypropyl cellulose content does not greatly influence PSE release. The SRMT contained only PSE and excipients, and were coated with a mixture of HPMC and the water-insoluble polymer ethylcellulose. The PSE release profile for the SRMT could be controlled by varying the thickness of the coat, and the lag time could be controlled by varying the amount of ethylcellulose present in the polymer coat. PSE was released immediately from our encapsulated mini-tablet system and release was sustained over an extended period of time: the PSE in the IRMT dissolved within 60min, whereas the PSE in the SRMT was released over 8-10h. This system can be modified to yield various extended drug-release profiles, thereby harnessing the benefits of both SRMT and IRMT.     

Development and in vitro evaluation of oral controlled release formulations of celecoxib using optimization techniques

The objective of this study was to develop controlled release matrix embedded formulations of celecoxib (CCX) as candidate drug using hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose (EC), either alone or in combination, using optimization techniques like polynomial method and composite design. This would enable development of controlled release formulations with predictable and better release characteristics in lesser number of trials. Controlled release matrix tablets of CCX were prepared by wet granulation method. The in vitro release rate studies were carried out in USP dissolution apparatus (paddle method) in 900 ml of sodium phosphate buffer (pH 7.4) with 1% v/v tween-80. The in vitro drug release data was suitably transformed and used to develop mathematical models using first order polynomial equation and composite design techniques of optimization. In the formulations prepared using HPMC alone, the release rate decreased as the polymer proportion in the matrix base was increased. Whereas in case of formulations prepared using EC alone, only marginal difference was observed in the release rate upon increasing the polymer proportion. In case of formulations containing combination of HPMC and EC, the release of the drug was found to be dependent on the relative proportions of HPMC and EC used in the tablet matrix. The release of the drug from these formulations was extended up to 21 h indicating they can serve as once daily controlled release formulations for CCX. Mathematical analysis of the release kinetics indicates a near approximate Fickian release character for most of the designed formulations. Mathematical equation developed by transforming the in vitro release data using composite design model showed better correlation between observed and predicted t(50%) (time required for 50% of the drug release) when compared to first order polynomial equation model. The equation thus developed can be used to predict the release characteristics of the drug from matrix embedded formulations depending upon the proportion of HPMC and EC used in the formulation.     

Physical characterization of HPMC and HEC and investigation of their use as pelletization aids

Pelletization of drugs with suitable excipients by extrusion/spheronization is one of the popular approaches in the development of solid dosage forms, especially for extended-release formulations. However, the choice of pelletization aids is limited to the use of microcrystalline cellulose (MCC), which is generally wet massed using water. In the formulation of water-sensitive drugs, however, pelletization excipients which may be wet massed using an organic liquid are desired. In the present study therefore, two cellulose ethers, hydroxypropyl methylcellulose (HPMC) and hydroxyethyl cellulose (HEC), were characterized for their physical properties, such as moisture content, bulk and tapped densities, median particle size and size distribution, surface area and surface morphology, in an attempt to evaluate the feasibility of their use as pelletization aids. Since HPMC and HEC are water-soluble, but insoluble in isopropyl alcohol, the latter was used as the wet massing liquid for pelletization. Microcrystalline cellulose, because of its established uniqueness as a pellet former, was used as the reference material and was also wet massed using isopropyl alcohol for consistency and comparison. Placebo pellets of the three cellulosic excipients, HPMC, HEC and MCC, were prepared by extrusion/spheronization. The placebo pellets were evaluated for their size and size distribution, hardness, friability, bulk and tapped densities and sphericity. Of the three cellulosic excipients, HPMC and MCC produced pellets with the most desirable attributes. In water as the dissolution medium, the HPMC pellets absorbed water and formed a single viscous gel matrix that slowly dissolved. HEC pellets were swollen but intact and slowly eroded, whereas MCC pellets stayed intact without dissolution or erosion. These findings indicate that HPMC will find application in pellet formulations of water-sensitive drugs, as well as in those formulations where water may not be used as wet massing liquid and an organic liquid must be used. It will also be a good choice as a pelletization excipient when complete water-solubility of all the formulation excipients is desired. It may be anticipated that modification of drug release from pelletized formulations may also be achieved by using cellulose ethers of varying viscosity grades and hydration rates.