Interpolymer complexation between copovidone and carbopol and its effect on drug release from matrix tablets

The interaction between copovidone and Carbopol 907 is pH dependent. When the pH of an aqueous solution fell below pH 4.5, a water-insoluble complex began to form and precipitate. This complex resulted from a hydrogen-bond-induced interaction between the carboxylic groups in Carbopol 907 and the carbonyl groups of N-vinylpyrrolidone repeat units in copovidone. Consisting of these two polymers at an approximate 1:1 weight ratio, the complex was an amorphous material with a glass transition temperature of 157?°C. The interpolymer complexation in situ was applied to modify drug release properties of Carbopol 907-based theophylline matrix tablets. The effect of copovidone on drug release was dependent on the pH of the dissolution medium. In a 0.1 N hydrochloride acid solution at pH 1.2 and 50?mM acetate buffer at pH 4.0, an insoluble tablet matrix was formed as a result of the in situ interpolymer complexation, and theophylline was released therefore via Fickian diffusion. In a 50?mM phosphate buffer at pH 6.8, drug release from the matrix tablets was still impacted by the in situ interpolymer complexation because of the low-pH microenvironment induced by Carbopol 907. As a result, drug release rate of the matrix tablet containing both polymers at pH 6.8 was slower than that of the matrix tablets containing individual polymers. We observed similar drug release rates at both pH 1.2 and pH 6.8 between tablets containing the physical blend of these two polymers and tablets containing preformed interpolymer complexes.     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

Studies on Drug Release Kinetics from Carbomer Matrices

The objective of this study is to gain a mechanistic understanding of drug release kinetics from directly compressed tablets containing Carbopol 934P and 974P resins. Carbopol resins belong to a family of carbomers which are synthetic, high molecular weight, non-linear polymers of acrylic acid, crosslinked with polyalkenyl polyether. They are currently being used as polymeric matrices for controlling drug release in pharmaceutical tablets. This investigation focuses on the influence of the type of drug and the pH of the dissolution media, along with other factors on the drug release kinetics from carbomer matrices. Directly compressed tablets were prepared using a Stokes single station laboratory press and blends of polymers and lactose with drugs like theophylline, norephedrine HCI, and chlorpheniramine maleate. In vitro. drug release studies from the tablets were performed according to USP method II. Drug release rates were obtained by plotting the fraction released versus time and data fitted to the equation:     

The effect of carboxymethyl chitin on sustained drug release of aspirin tablet

Carboxymethyl chitin (CM-chitin) was prepared at room temperature and characterized using ¹H NMR, FTIR and elemental analysis methods. The prepared CM-chitin was then used as a hydrophilic matrix for the preparation of the aspirin sustained release tablets via the wet granulation technique. The aspirin release profiles of the prepared tablets in a simulated gastric fluid and simulated intestinal fluid, respectively, were studied with the rotating-basket dissolution method. The results showed that the aspirin release rate in simulated gastric fluid was lower than that in simulated intestinal fluid. Thus, CM-chitin proved to be a pH-sensitive hydrophilic matrix.     

Effects of manufacturing process variables on in vitro dissolution characteristics of extended-release tablets formulated with hydroxypropyl methylcellulose

The purpose of this study was to investigate the effect of three process variables: distribution of hydroxypropyl methylcellulose (HPMC) within the tablet matrix, amount of water for granulation, and tablet hardness on drug release from the hydrophilic matrix tablets. Tablets were made both by direct compression as well as wet granulation method. Three formulations were made by wet granulation, all three having the exact same composition but differing in intragranular:intergranular HPMC distribution in the matrix. Further, each formulation was made using two different amounts of water for granulation. All tablets were then compressed at two hardness levels. Dissolution studies were performed on all tablets using USP dissolution apparatus I (basket). The dissolution parameters obtained were statistically analyzed using a multilevel factorial-design approach to study the influence of the various process variables on drug release from the tablets. Results indicated that a change in the manufacturing process could yield significantly dissimilar dissolution profiles for the same formulation, especially at low-hardness level. Overgranulation could lead to tablets showing hardness-dependent drug-release characteristics. Studies showed that intergranular addition of a partial amount of HPMC (i.e., HPMC addition outside of granules) provided a significant advantage in making the formulation more robust over intragranular addition (i.e., that in which the entire amount of HPMC was added to the granules). Dissolution profiles obtained for these tablets were relatively less dependent on tablet hardness irrespective of the amount of water added during granulation.     

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.     

Fabrication and in vitro evaluation of bidirectional release and stability studies of mucoadhesive donut-shaped captopril tablets

Objective: To obtain controlled release of captopril in the stomach, coated, mucoadhesive donut-shaped tablets were designed.

Materials and methods: Donut-shaped tablet were made of different ratios of diluents to polymer or combination of polymers by direct compression method. Top and bottom portions of the tablet were coated with water-insoluble polymer followed by mucoadhesive coating. Time of water penetration, measurement of tensile strength, mucoadhesion studies (static ex vivo and ex vivo wash-off) were taken into account for characterization of respective films. In vitro study has been performed at different dissolution mediums. Optimized batches were also prepared by wet granulation. Stability studies of optimized batches have been performed.

Results: The results of time of water penetration and tensile strength indicated positive response against water impermeation. Mucoadhesive studies showed that film thickness of 0.12?mm was good for retention of tablet at stomach. At pH 1.2, optimized batch of tablet made with hydroxypropyl methyl cellulose (HPMC) E15 as binder showed 80% w/w drug release within 4–5?h with maximum average release of 97.49% w/w. Similarly, maximum average releases of 96.36% w/w and 95.47% w/w were obtained with nearly same dissolution patterns using combination of HPMC E5 and HPMC E50 and sodium salt of carboxy methyl cellulose (NaCMC) 500–600 cPs instead of HPMC E15. The release profiles in the distilled water and pH 4.5 followed the above pattern except deviation at pH 6.8. Stability studies were not positive for all combinations.

Conclusion: Coated, mucoadhesive donut-shaped tablet is good for controlled release of drug in the stomach.     

Effect of formulation and process variables on the release behavior of amoxicillin matrix tablets

The sustained release of amoxicillin is desired to be confined to the upper gastrointestinal tract to treat certain kind of infections. In vitro dissolution, at pH 1.2, of amoxicillin sustained release tablets has been studied varying the proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water proportion in the granulation fluid. M_t, the amount of drug released at time (t) and defined in terms of the total drug released over a long time period (M_inf), was described by M_t/M_inf = ktⁿ. Matrices with increasing proportions of sodium alginate showed increasing values of the exponent indicative of the release mechanism (n) and increasing release constant values (k). This is attributed to a drop in the coherence of the polymeric matrix with increasing alginate proportions that produces an increasing polymer relaxation and erosion. Decreasing Carbopol 971P NF proportions reduce the amount of dissolved polymer during granulation, producing a lesser obstruction of amoxicillin dissolution. Alginate proportions of 80% produce near zero order release profiles. Granules obtained with increasing ethanol proportions showed increasing release constant values and a minor change in the exponent (n) values. This is considered a result of lower polymer dissolution during granulation that allows a lesser matrix coherence and a greater amoxicillin dissolution. Alginate matrices granulated with different ethanol/water proportions showed no significant changes in the amoxicillin release profile. There is a trend toward increasing floating times with increasing Carbopol 971P NF proportions.     

Formulation and Stability Evaluation of Ketoprofen Sustained-Release Tablets Prepared by Fluid Bed Granulation with Carbopol® 971P Solution

ABSTRACT

The objectives of the present study were: (1) to investigate the possibility of using a Carbopol polymeric solution as granulating agent by the fluid bed granulating process; (2) to select a suitable method of tabletting for sustaining the release of ketoprofen for 12 hr; (3) to perform stability studies according to International Committee on Harmonization (ICH) guidelines and photostability on ketoprofen SR tablets; (4) to study the influence of the storage conditions on release kinetics and melting endotherm of ketoprofen; and (5) to predict the shelf-life of the ketoprofen SR tablets. Tabletting ingredients were ketoprofen, anhydrous dicalcium phosphate, Carbopol® 971P, talc, and magnesium stearate. Carbopol® 971P solution (0.8% w/v) was used as a granulating solution in the fluid bed granulator. For comparative evaluation, tablets were also prepared by direct compression and wet granulation, and subjected to dissolution. Tablets prepared by fluid bed granulation technique were stored in incubators maintained at 37, 40, 50, and 60°C, 40°C/75% RH, 30°C/60% RH, and 25°C/60% RH, and in a light chamber with light intensity of 600 ft candle at 25°C. Melting endotherms were obtained for the drug as well as the tablets during stability studies by differential scanning calorimetry. Tablets prepared by fluid bed granulation technique prolonged the release of ketoprofen better than tablets obtained by direct compression and wet granulation. Further, it complied with the requirements of ICH guidelines for stability testing. Higher temperature and humidity (40 ± 2°C/75% RH, 40°C, 50°C, and 60°C) adversely affected the rate and extent of the dissolution. Ketoprofen SR tablets stored in amber-colored bottles demonstrated a good photostability for 6 months at 600 ft candle. The shelf-life of the formulation was predicted as 32 months.     

Effect of Sodium Bicarbonate on the Properties of Metronidazole Floating Matrix Tablets

The effect of sodium bicarbonate (SB) on the swelling behavior and the sustained release of floating systems was studied with varied proportions of this excipient and metronidazole. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. Under in vitro dissolution conditions, the addition of SB to metronidazole sustained-release tablets modifies the matrix hydration volume, increasing at the beginning, reaching a maximum, and then declining. Pure Carbopol matrices show a rapid hydration with a limited further effect of the SB and metronidazole loads. Methocel show a significant increase of the apparent hydration volume due to SB addition with no further notable change due to metronidazole load. Increasing the metronidazole load reduces the floating time of Carbopol matrices while no effect on Methocel matrices could be observed within 8 hours dissolution. Matrices show increasing release constant values (k) as the metronidazole load increases. Methocel matrices release the drug 10% to 15% faster than Carbopol matrices. SB increases the cumulative amount of drug released from Methocel but not that releasing from Carbopol. These results are attributed to the intrinsic polymer properties, the barrier effect of CO₂ bubbles, and the matrix volume expansion produced after addition of SB.     

Quality-by-design approach for the development of telmisartan potassium tablets

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis^® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis^® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis^® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis^® tablets in beagle dogs.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Spray-dried O-carboxymethyl chitosan as potential hydrophilic matrix tablet for sustained release of drug

Objective: The aim of the present investigation was to evaluate the use of spray-dried O-carboxymethyl chitosan (OCMCS) as potential hydrophilic matrix excipient for sustained release of drug.

Methods: The polymer was synthesized from chitosan, then spray-dried and characterized. Tablets with different OCMCS concentrations (80, 50, 30, 5 and 2% w/w), containing diltiazem (DTZ) as model drug, were prepared for direct compression (DC) and after the wet granulation method (WG).

Results: The spray-dried OCMCS powder was spherical, with a smooth surface and an average size of 2.2?µm. The tablets prepared for WG disintegrated in time less than 30?min. The tablets obtained for DC presented high retention of the drug, with zero order or Higuchi release kinetic. There was a direct relationship between the OCMCS concentration and the release ratio, swelling degree and water uptake behavior. DC tablets containing 80% OCMCS presented behavior as an effective swelling-control system. The DC tablets with 5% OCMCS showed a similar release profile at formulations with 30% HPMC.

Conclusion: Spray-dried OCMCS showed great potential as hydrophilic matrices for drug-sustained release.     

Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies

Background: Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications. Method: The core tablets of rabeprazole sodium were prepared using organic wet granulation method. Multiparticulates of lansoprazole and esomeprazole magnesium were prepared through drug layering of sugar spheres, using powder layering and suspension layering methods, respectively. Tablets and drug-layered multiparticulates were seal-coated, followed by delayed release film coating application, using Acryl-EZE®, aqueous acrylic enteric system. Multiparticulates were then filled into capsules. The final dosage forms were evaluated for physical properties, as well as in vitro dissolution testing in both compendial acid phase, 0.1N HCl (pH 1.2), and intermediate pH, acetate buffer (pH 4.5), followed by phosphate buffer, pH 6.8. The stability of the delayed release dosage forms was evaluated upon storage in accelerated conditions [40°C/75% relative humidity] for 3 months. Results: All dosage forms demonstrated excellent enteric protection in the acid phase, followed by rapid release in their respective buffer media. Moreover, the delayed release dosage forms remained stable under accelerated stability conditions for 3 months. Conclusions: Results showed that Acryl-EZE enteric coating systems provide excellent performance in both media (0.1N HCl and acetate buffer pH 4.5) for monolithic and multiparticulate dosage forms.     

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development

Objective: The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. Methods: The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. Results: The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. Conclusions: The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.     

Production of advanced solid dispersions for enhanced bioavailability of itraconazole using KinetiSol® Dispersing

Objectives: To investigate the ability of KinetiSol® Dispersing to prepare amorphous solid dispersions of itraconazole using concentration-enhancing polymers. Methods: Concentration-enhancing nature of several cellulosic polymers (HPMC, hypromellose acetate succinate) was studied using a modified in vitro dissolution test. Solid dispersions were prepared by KinetiSol® Dispersing and characterized for solid-state properties using X-ray diffraction and differential scanning calorimetry. Potency and release characteristics were also assessed by high-performance liquid chromatography. Oral bioavailability of lead formulations was also assessed in animal models. Results: Screening studies demonstrated superior concentration-enhancing performance from the hypromellose acetate succinate polymer class. Data showed that stabilization was related to molecular weight and the degree of hydrophobic substitution on the polymer such that HF > MF ≈ LF, indicating that stabilization was achieved through a combination of steric hindrance and hydrophobic interaction, supplemented by the amphiphilic nature and ionization state of the polymer. Solid dispersions exhibited amorphous solid-state behavior and provided neutral media supersaturation using a surfactant-free pH change method. Rank-order behavior was such that LF > MF > HF. Addition of Carbopol 974P increased acidic media dissolution, while providing a lower magnitude of supersaturation in neutral media because of swelling of the high viscosity gel. In vivo results for both lead compositions displayed erratic absorption was attributed to the variability of gastrointestinal pH in the animals. Conclusions: These results showed that production of amorphous solid dispersions containing concentration-enhancing polymers through KinetiSol® Dispersing can provide improved oral bioavailability; however, additional formulation techniques must be developed to minimize variability associated with natural variations in subject gastrointestinal physiology.     

Formulation and stability evaluation of ketoprofen sustained-release tablets prepared by fluid bed granulation with Carbopol 971P solution

The objectives of the present study were: (1) to investigate the possibility of using a Carbopol polymeric solution as granulating agent by the fluid bed granulating process; (2) to select a suitable method of tabletting for sustaining the release of ketoprofen for 12 hr; (3) to perform stability studies according to International Committee on Harmonization (ICH) guidelines and photostability on ketoprofen SR tablets; (4) to study the influence of the storage conditions on release kinetics and melting endotherm of ketoprofen; and (5) to predict the shelf-life of the ketoprofen SR tablets. Tabletting ingredients were ketoprofen, anhydrous dicalcium phosphate, Carbopol® 971P, talc, and magnesium stearate. Carbopol® 971P solution (0.8% w/v) was used as a granulating solution in the fluid bed granulator. For comparative evaluation, tablets were also prepared by direct compression and wet granulation, and subjected to dissolution. Tablets prepared by fluid bed granulation technique were stored in incubators maintained at 37, 40, 50, and 60°C, 40°C/75% RH, 30°C/60% RH, and 25°C/60% RH, and in a light chamber with light intensity of 600 ft candle at 25°C. Melting endotherms were obtained for the drug as well as the tablets during stability studies by differential scanning calorimetry. Tablets prepared by fluid bed granulation technique prolonged the release of ketoprofen better than tablets obtained by direct compression and wet granulation. Further, it complied with the requirements of ICH guidelines for stability testing. Higher temperature and humidity (40 ± 2°C/75% RH, 40°C, 50°C, and 60°C) adversely affected the rate and extent of the dissolution. Ketoprofen SR tablets stored in amber-colored bottles demonstrated a good photostability for 6 months at 600 ft candle. The shelf-life of the formulation was predicted as 32 months.     

Effect of Added Pharmatose DCL11 on the Sustained-Release of Metronidazole From Methocel K4M and Carbopol 971P NF Floating Matrices

ABSTRACT

In vitro dissolution of metronidazole from sustained release floating tablets was studied with varied proportions of sodium bicarbonate (SB) and Pharmatose DCL 11. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. The variables studied include the matrices' release profile, hydration volume, and floating behavior. All Methocel matrices floated more than 8 h with SB proportions up to 24%, while Carbopol matrices floated more than 8 h with SB proportions only up to 12%. Matrices' hydration increased with time until reaching a peak and declining thereafter. Methocel matrices showed greater hydration volumes and greater drug dissolution compared to Carbopol matrices. After adding increasing quantities of Pharmatose to matrices containing 12% SB, hydration volume decreased while dissolution increased. These results were attributed to water-filled pores that formed following the Pharmatose dissolution and to reduced polymer proportions. Carbopol matrices showed greater susceptibility to the added Pharmatose, becoming more erodible and releasing higher quantities of metronidazole. The greater Carbopol susceptibility to added Pharmatose was attributed to its faster hydration. Methocel matrices hydrate rapidly only at the surface, delaying hydration and Pharmatose dissolution.     

Evaluation of various processes for simultaneous complexation and granulation to incorporate drug–cyclodextrin complexes into solid dosage forms

Insoluble drugs often formulated with various excipients to enhance the dissolution. Cyclodextrins (CDs) are widely used excipients to improve dissolution profile of poorly soluble drugs. Drug–CD complexation process is complex and often requires multiple processes to produce solid dosage form. Hence, this study explored commonly used granulation processes for simultaneous complexation and granulation. Poorly soluble drugs ibuprofen and glyburide were selected as experimental drugs. Co-evaporation of drug:CD mixture from a solvent followed by wet granulation with water was considered as standard process for comparison. Spray granulation and fluid bed processing (FBP) using drug:CD solution in ethanol were evaluated as an alternative processes. The dissolution data of glyburide tablets indicated that tablets produced by spray granulation, FBP and co-evaporation–granulation have almost identical dissolution profile in water and 0.1% SLS (>70% in water and >60% in SLS versus 30 and 34%, respectively for plain tablet, in 120?min). Similarly, ibuprofen:CD tablets produced by co-evaporation–granulation and FBP displayed similar dissolution profile in 0.01?M HCl (pH 2.0) and buffer pH 5.5 (>90 and 100% versus 44 and 80% respectively for plain tablets, 120?min). Results of this study demonstrated that spray granulation is simple and cost effective process for low dose poorly soluble drugs to incorporate drug:CD complex into solid dosage form, whereas FBP is suitable for poorly soluble drugs with moderate dose.     

Disintegration and Dissolution Parameters of Compressed Tablets Prepared by Direct Compression-Wet Granulation Process and Compression of Wet Granulation of Both Sections

Abstract

Hardness, disintegration and dissolution of compressed tablets were assessed by compressing tablets from granulations prepared by dry and wet granulation process of two sections and by composite wet granulation process. Modified USP XVIII apparatus for disintegration, rotating basket apparatus USP XVIII and constant circulation apparatus were employed for measuring dissolution. The constant circulation apparatus was used in the studies as only it proved to be sensitive to reflect the differences in the dissolution rates and was a close analog of physiological situation. Four types of tablets containing acetylsalicylic acid, codeine phosphate and propoxyphene hydrochloride were prepared. Tablets prepared by partial dry and wet granulation process did not show significant differences in the rates of dissolution as compared to those prepared by complete wet granulation process.