Quality by design: understanding the formulation variables of a cyclosporine A self-nanoemulsified drug delivery systems by Box-Behnken design and desirability function

Quality by design (QBD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A very useful component of the QBD is the understanding of factors and their interaction effects by a desired set of experiments. The present project deals with a case study to understand the effect of formulation variables of nanoemulsified particles of a model drug, cyclosporine A (CyA). A three-factor, three-level design of experiment (DOE) with response surface methodology (RSM) was run to evaluate the main and interaction effect of several independent formulation variables that included amounts of Emulphor El-620 (X(1)), Capmul MCM-C8 (X(2)) and 20% (w/w) CyA in sweet orange oil (X(3)). The dependent variables included nanodroplets size (Y(1)), nanoemulsions turbidity (Y(2)), amounts released after 5 and 10min (Y(3), Y(4)), emulsification rate (Y(5)) and lag time (Y(6)). A desirability function was used to minimize lag time and to maximize the other dependent variables. A mathematical relationship, Y(5)=9.09-0.37X(1)+0.37X(2)-0.45X(3)+0.732X(1)X(2)-0.62X(1)X(3)+0.3X(2)X(3)+0.02X(1)(2)-0.28X(2)(2)+0.471X(3)(2) (r(2)=0.92), was obtained to explain the effect of all factors and their colinearities on the emulsification rate. The optimized nanodroplets were predicted to yield Y(1), Y(2), Y(3), Y(4), Y(5) and Y(6) values of 42.1nm, 50.6NTU, 56.7, 107.2, 9.3%/min and 3.5min, respectively, when X(1), X(2), and X(3) values were 36.4, 70 and 10mg, respectively. A new batch was prepared with these levels of the independent variables to yield Y(1)-Y(6) values that were remarkably close to the predicted values. In conclusion, this investigation demonstrated the potential of QBD in understanding the effect of the formulation variables on the quality of CyA self-nanoemulsified formulations.     

Design and in vitro evaluation of a bipolymeric delivery device for the amelioration of colonic diseases using a popular glucocorticoid as a model drug

The present investigation concerns with the development and optimization of a bipolymeric delivery device for the treatment of colonic diseases. Prednisolone - a popular glucorticoid was used a model drug. The formulations were designed with an objective to deliver the drug to the large bowel with a minimal release in the upper part of the gastrointestinal tract. Amount of Eudragit RS100 (X1) and amount of Guar gum (X2) were the two variables used to characterize and optimize the formulation. Three dependant variablescumulative drug release at 60 min (Y60), at 240 min (Y240) and at 480 min (Y480) were considered as optimization factors. The results were analyzed statistically and a p <0.01 was considered to be statistically significant. Three dimensional response surface plots were drawn and the impacts of the independent variables on the chosen variables were analyzed and optimized.     

Optimization and characterization of controlled release multi-particulate beads coated with starch acetate

The objectives of the present study were (1) to model the effects of process and formulation variables on in vitro release profile of a model drug dyphylline from multi-particulate beads coated with starch acetate (SA); (2) to validate the models using R2 and lack of fit values; (3) to optimize the formulation by response surface methodology (RSM); (4) to characterize the optimized product by thermal, X-ray and infrared spectroscopic analyses. Dyphylline loaded inert beads were coated using organic solution of SA with high degree of substitution. A three-factor, three-level Box-Behnken design was used for the optimization procedure with coating weight gain (X1), plasticizer concentration (X2) and curing temperature (X3) as the independent variables. The regression equation generated for Y5 (cumulative percent drug released after 12 h) was Y5 = 89.83-11.98X1 + 2.82X2 - 4.31X1(2) + 1.90X1X2. Optimization was done by maximizing drug release in 12 h and placing constraints at dissolution time points of 0.5, 1, 4 and 8 h. The drug release data of the optimized product were close to that predicted by the model. The models could explain 99% of variability in responses. Thermal, X-ray and infrared analyses suggested absence of any significant interaction of the drug with the excipients used in the formulation. SEM photographs showed the integrity of the coating layer.     

Response Surface Methodology to Obtain β-Estradiol Biodegradable Microspheres for Long-Term Therapy of Osteoporosis

The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of β-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was:

Y1 = ?129.85 + 29.35X₁ + 129.99X₂ + 64.82X₃ ? 3.2X₁X₂ ? 0.29X₁X₃ ? 35.83X₂X₃ ? 2.05X₁² ? 13.23X₂² ? 5.92X₃² (R2 = 0.99)

The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases β-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.     

Response surface methodology to obtain beta-estradiol biodegradable microspheres for long-term therapy of osteoporosis

The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of beta-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was: Y1 = -129.85 + 29.35X1 + 129.99X2 + 64.82X3 - 3.2X1X2 - 0.29X1X3 - 35.83X2X3 - 2.05X(2)(1) - 13.23X(2)(2) - 5.92X(2)(3) (R2 = 0.99) The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases beta-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.     

Influence of beta-cyclodextrin complexation on glipizide release from hydroxypropyl methylcellulose matrix tablets

Glipizide was complexed with beta-cyclodextrin in an attempt to enhance the drug solubility. The phase solubility diagram was classified as A(L) type, which was characterized by an apparent 1:1 stability constant that had a value of 413.82 M(-1). Fourier transform infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry and proton nuclear magnetic resonance spectral analysis indicated considerable interaction between the drug and beta-cyclodextrin. A 2(3) factorial design was employed to prepare hydroxypropyl methylcellulose (HPMC) matrix tablets containing the drug or its complex. The effect of the total polymer loads (X1), levels of HPMC K100LV (X9), and complexation (X3) on release at first hour (Y1), 24 h (Y2), time taken for 50% release (Y3), and diffusion exponent (Y4) was systematically analyzed using the F test. Mathematical models containing only the significant terms (P < 0.05) were generated for each parameter by multiple linear regression analysis and analysis of variance. Complexation was found to exert a significant effect on Y1, Y2, and Y3, whereas total polymer loads significantly influenced all the responses. The models generated were validated by developing two new formulations with a combination of factors within the experimental domain. The experimental values of the response parameters were in close agreement with the predicted values, thereby proving-the validity of the generated mathematical models.     

Theoretical and experimental investigations into the delamination tendencies of bilayer tablets

A controlled release resinate beads of betahistine diHCl (BHCl), a short half-life freely water soluble drug, was developed to allow once-daily administration to improve patient compliance and eliminate the risk of intolerance of the drug. BHCl-resin complex was subsequently coated with Eudragit RS100. A 2(4) full factorial design was employed for optimization and to explore the effect of Eudragit RS100 concentration in the coating solution (X(1)), the coating percentage (X(2)), the speed of rotation (X(3)) and the concentration of plasticizer (PEG 400) (X(4)) on the release rate of the drug from the microcapsules. The extent of coating (Y(1)), and the percentage drug released at given times (Y(2), Y(3) and Y(4)) were selected as dependent variables. The optimization process was performed for X(1), X(2), X(3) and X(4) using target ranges of these responses determined based on target release model deduced form zero-order dissolution profile of BHCl for once-daily administration. The levels of X(1), X(2), X(3) and X(4) of optimized BHCl microcapsules are 14.42%, 50.63%, 1495rpm and 9.94%, respectively. The calculated value of f(2) for the optimized BHCl microcapsules filled into hard gelatin capsules was 67.03 indicating that the dissolution profiles of the optimized formulation is comparable to that of the target release model. It could be concluded that a promising once-daily extended-release microcapsules of the highly water soluble drug, BHCl, was successfully designed.     

Release modulating hydrophilic matrix systems of losartan potassium: optimization of formulation using statistical experimental design.

The aim of the present research work was to systemically device a model of factors that would yield an optimized sustained release dosage form of an anti-hypertensive agent, losartan potassium, using response surface methodology by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the amount of the release retardant polymers - HPMC K15M (X(1)), HPMC K100M (X(2)) and sodium carboxymethyl cellulose (X(3)). The dependent variables were the burst release in 15 min (Y(1)), cumulative percentage release of drug after 60 min (Y(2)) and hardness (Y(3)) of the tablets with constraints on the Y(2)=31-35%. Statistical validity of the polynomials was established. In vitro release and swelling studies were carried out for the optimized formulation and the data were fitted to kinetic equations. The polynomial mathematical relationship obtained Y(2)=32.91-2.30X(1)-5.69X(2)-0.97X(3)-0.41X(1)X(2)+0.21X(1)X(3)-0.92X(1)(2)-1.89X(2)(2) (r(2)=0.9944) explained the main and quadratic effects, and the interactions of factors influencing the drug release from matrix tablets. The adjusted (0.9842) and predicted values (0.9893) of r(2) for Y(2) were in close agreement. Validation of the optimization study indicated high degree of prognostic ability of response surface methodology. Tablets showed an initial burst release preceding a more gradual sustained release phase following a non-fickian diffusion process. The Box-Behnken experimental design facilitated the formulation and optimization of sustained release hydrophilic matrix systems of losartan potassium.     

Optimisation of polyherbal gels for vaginal drug delivery by Box-Behnken statistical design.

The present research work aimed at development and optimisation of mucoadhesive polyherbal gels (MPG) for vaginal drug delivery. As the rheological and mucoadhesive properties of the gels correlate well to each other the prepared MPGs were optimised for maximum mucoadhesion using a relationship between the storage modulus (G') and Gel Index (GI), by employing a 3-factor, 3-level Box-Behnken statistical design. Independent variables studied were the polymer concentration (X(1)), honey concentration (X(2)) and aerosil concentration (X(3)). Aerosil has been investigated for the first time to improve the consistency of gels. The dependent variables studied were the elastic modulus, G'(Y(1)), gel index (Y(2)), and maximum detachment force (Y(3)) with applied constraints of 500相似文献   

Optimizing the formulation of procationic liposomes-protamine-DNA complexes by response surface methodology

The procationic liposomes-protamine-DNA (PLPD) vectors we described here are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA and procationic liposomes made of phospholipids, cholesterol, and CHETA (Cholest-5-en-3beta-yl[2-[[4-[(carboxymethyl)dithio]-1-iminobutyl]amino]ethyl] carbamate, C36H61N3O4S2). Response surface methodology (RSM) was employed to optimize the formulation of PLPD. A three-factor, five-level RSM design was used for the optimization procedure, with the weight ratio of protamine/DNA (X1), the molar percent of CHETA (X2), and the weight ratio of CHETA/DNA (X3) in the procationic liposomes as the independent variables. PLPD size (Y1) and PLPD transfectivity (Y2) that was quantified as mU of beta-galactosidase per milligram of total protein were response variables. The simple factor experiment was utilized to define the experimental design region, and therefore the responses for the 15 formulations were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The mathematical model predicted the optimized levels of X1, X2, and X3 through which the desired particle size and transfectivity were achieved. According to these levels, an optimized PLPD formulation was prepared, resulting in a particle size of 228.9 +/- 8.0 nm and transfectivity of 24.26 +/- 2.60 mU beta-galactosidase/mg protein.     

胶束薄层色谱法同时测定APC片中3组分含量

应用胶束薄层色谱法同时测定复方乙酰水杨酸片 (APC)中的阿司匹林 (A)、非那西汀 (P)和咖啡因 (C)的含量。在聚酰胺薄膜上 ,以 2 %SDS 乙腈 NaAc Na2 HPO4 ·1 2H2 O(3∶1∶1 )为展开剂 ,测定波长为 2 73nm ,单波长反射法锯齿扫描 ,结果 ,点样量在 0 9～ 4 5 μg,A组分的点样量X(mi)与斑点积分面积的比值Y(Ai/As)呈良好的线性关系 ,其回归方程为 :Y =2 0 0 3 1X +0 81 5 9,r =0 9981 ,平均回收率为 1 0 1 3 % ,RSD 1 9% ;点样量在 0 6～ 3 0 μg,P组分的回归方程为 :Y =1 2 1 4 5X +0 4 1 0 6,r=0 9978,平均回收率为 99 2 % ,RSD 2 4 % ;点样量在 0 1 4～ 0 7μg,C组分的回归方程为 :Y =2 1 3 63X +0 64 5 2 ,r=0 9984 ,平均回收率为 :98 4 % ,RSD 3 1 %     

Naproxen-Eudragit microspheres: screening of process and formulation variables for the preparation of extended release tablets

The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on the rate of drug release. The response variable was cumulative percent of naproxen dissolved in 12 h in simulated intestinal fluid with constraints on responses that included percent yield, hardness, thickness, and the angle of repose. Mathematical relationship for percent of naproxen dissolved in 12 h (Y5) with various factors yielded the following polynomial equation; Y5 (% dissolved in 12 h) = 95.48 + 0.53 X1 + 3.51 X2 + 3.84 X3 - 3.80 X4 - 2.46 X5 - 2.90 X6 - 3.91 X7. The results showed that all the seven factors affected, with varying order, the release of naproxen from its compressed tablets.     

Optimization of formulation components and characterization of large respirable powders containing high therapeutic payload

The aim of the study was to optimize and characterize high therapeutic payload large respirable powders prepared by spray-drying technique for maximum fine particle fraction with minimum quantities of excipients. Influence of formulation components was optimized by a three-factor, five-level central composite design having different proportions of L-leucine (X1), tobramycin sulfate (X2), and poloxamer-188 (X3) as the independent variables and fine particle fraction as a response variable (Y). Large respirable powders were characterized for particle size, size distribution, moisture, crystallinity, and morphology. In vitro aerosol performance of powders was determined by an eight-stage Andersen cascade impactor using the Rotahaler. Mathematical model elucidated for Y was Y = 56.2068 + 5.7481 X1 - 3.0531 X2 + 0.8468 X3 + 1.1737 X1 X2 - 0.5012 X1 X3 - 0.7412 X2 X3 - 0.7149 X1(2) - 1.9212 X2(2) - 1.6187X3(2). The component of greatest influence on product performance (response variable) was found to be L-leucine. Lack of fit was not significant (p = 0.08), and regression equation predicted response for Y was in reasonably good agreement with experimental values (p = 0.01; R2 = 0.92). The optimal model predicted with a fine particle fraction of 62.8 +/- 2.6% with X1, X2, X3 levels of 20, 45.71, and 5.51 respectively. Large respirable powders with TB load of 45.7% w/w were prepared; they had smooth surface texture, dimpled spherical shape, roundness value close to 1(1.048 +/- 0.032) and were found to possess bulk tap densities of 0.04 g/cc, geometric particle sizes of 6-7 micro m, and emitted dose of 92%. The results of the studies suggest that in vitro aerosol performance was affected significantly by small and deliberate change of specific formulation components and its proportions. It may be concluded that appropriate type and proportion of excipients is necessary to obtain maximum fine particle fraction of large respirable powders containing high therapeutic payloads.     

硫酸沙丁胺醇口腔崩解片的制备及质量评价

目的：优选硫酸沙丁胺醇口崩片直压工艺,并测定其含量。方法：采用因子设计优选口崩片直压工艺,以直压甘露醇（pearlitol 200 DC）（X1）、交联聚维酮（PVPP）（X2）、微粉硅胶（silicon dioxide）（X3）、硬脂酸镁（MS）（X4）为自变量,以直压粉末的休止角（angle of repose）（Y1）、片子硬度（Hardness）（Y2）以及崩解时限（Disintegration）（Y3）为变量建立方程,最终确定直压工艺;采用反相高效液相色谱法测定样品含量。结果：X1、X3显著影响Y1,方程为Y1=35．8375—0．03125X1＋0．4X3-0．0425X1X3;X4显著影响Y2,方程为Y2=5．73875—0．54125X4;X2、X4显著影响Y3,方程为Y3=75—1．975X2＋20．375X4,通过等值线确定最佳处方,并且最佳处方的理论预测值在真实值波动范围内;硫酸沙丁胺醇在4～200ug／ml范围内线性良好,回收率为99．6％,RSD值为0．62％（n=9）。结论：硫酸沙丁胺醇直压工艺简便可行,建立的反相高效液相色谱法可用于硫酸沙丁胺醇口崩片的含量测定。     

Formulation of sublingual promethazine hydrochloride tablets for rapid relief of motion sickness

The delivery of antihistaminic agents via the oral route is problematic, especially for elderly patients. This study aimed to develop a sublingual formulation of promethazine hydrochloride by direct compression, and to mask its intensely bitter taste. Promethazine hydrochloride (PMZ) sublingual tablets prepared by direct compression were optimized using Box-Behnken full factorial design. The effect of a taste-masking agent (Eudragit E 100, X1), superdisintegrant (crospovidone; CPV, X2) and lubricant (sodium stearyl fumarate; SSF, X3) on sublingual tablets’ attributes (responses, Y) was optimized. The prepared sublingual tablets were characterized for hardness (Y1), disintegration time (Y2), initial dissolution rate (IDR; Y3) and dissolution efficiency after 30 min (Dissolution Efficiency (DE); Y4). The obtained results showed a significant positive effect of the three independent factors on tablet hardness (P < 0.05), and the interactive effect of Eudragit E 100 and CPV on tablet hardness was significant. Disintegration time was mainly affected by Eudragit E 100 and CPV concentrations. Moreover, IDR was employed to assess the taste masking effect, lower values were obtained at higher Eudragit E 100 concentration despite it was statistically insignificant (p > 0.05). Optimized formulation that was suggested by the software was composed of: Eudragit E 100 (X1) = 2.5% w/w, CPV (X2) = 4.13% w/w, and SSF (X3) = 1.0% w/w. The observed values of the optimized formula were found to be close to the predicted optimized values. The Differential Scanning Calorimetric (DSC) studies indicated no interaction between PMZ and tablet excipients.     

双氢埃托啡的燐光测定法及其应用

用药物—染料生成复合物的原理,建立了双氢埃托啡的燐光分析法?椒槊?可检测2ng。适用于动物血药、脑药分析。兔im0.1,0.2,1mg/kg双氢埃托啡后1与5min。血药,脑药与剂量成比例关系,其回归方程为:血药:Y=100.6X+17.73(1min), Y=367.8X+4.34(5min); 脑药:Y=5363 X+275.4(1 min),Y=6084 X+1022(5 min) 式中Y=药物浓度(ng/ml血或ng/g脑),X=双氢埃托啡剂量(mg/kg)。     

Hydrophilic matrices: application of Placket-Burman screening design to model the effect of POLYOX-carbopol blends on drug release

The aim of the present study was to screen the effect of seven factors--POLYOX molecular weight (X(1)) and amount (X(2)); carbopol (X(3)), lactose (X(4)), sodium chloride (X(5)), citric acid (X(6)); compression pressure (X(7))--on (1) the release of theophylline from hydrophilic matrices, demonstrated by changes in dissolution rate, and (2) their impact on the release exponent [n] indicative of the drug transport mechanism through the diffusion matrix. This objective was accomplished utilizing the Placket-Burman screening design. Theophylline tablets were prepared according to a 7-factor-12-run statistical model and subjected to a 24-h dissolution study in phosphate buffer at pH 7.2. The primary response variable, Y(4), was the cumulative percent of theophylline dissolved in 12h. The regression equation for the response was Y(4)=66.2167 - 17.5833X(1) - 3.3833X(2) - 9.366X(3) - 1.1166X(4) - 0.6166X(5) + 2.6X(6) - 2.783X(7). This polynomial model was validated by the ANOVA and residual analysis. The results showed that only two factors (X(2) and X(3)) had significant effect (p-value<0.10) on theophylline release from the hydrophilic polymer matrix. Factors (X(2) and X(7)) had significant effect (p-value<0.10) on [n], the exponent.     

Response surface methodology to obtain naproxen controlled release tablets from its microspheres with Eudragit L100-55

PURPOSE: Naproxen CR tablets have been obtained from its microspheres prepared by coprecipitation with Eudragit L100-55. The purpose of this work was to evaluate the main and interaction effects of deaggregating agent concentration (X1), compression pressure (X2) and amount of precipitating water (X3) on naproxen release. A secondary purpose was to obtain an optimized naproxen controlled release solid oral dosage form with a predictable 12 h drug release. METHOD: Eudragit L100-55 (10 g) was dissolved in 100 ml of ethyl alcohol, and 30g of naproxen was dispersed in it with stirring. Purified water (100mL, cooled to 4 degrees C) containing calcium chloride as a deaggregating agent was added to an alcoholic solution and homogenized. The mixture was filtered to obtain microspheres. Drug content analysis was performed spectrophotometrically at 332 nm. Tablets were prepared by compressing microspheres containing 500mg of naproxen after adding 1% magnesium stearate. Dissolution was performed by the USP specifications of naproxen tablets. A 3-factor 3-level Box-Behnken design was employed to get 15 experimental runs. The independent variables used were X1, X2 and X3. The dependent variables were dissolution at different time points with constraints on yield value and angle of repose of the microspheres, and hardness and thickness of the tablets. The dissolution constraints were placed such that the naproxen is released for 12 h by Higuchi's square root of time kinetics. RESULTS: The mathematical relationship obtained between X1, X2, X3 and the cumulative per cent of naproxen dissolved in 12 h with various constraints (Y5) was Y5 = 92.39 - 1.13X1 - 4.84X2 - 2.12X3 - 2.26X1X2 - 0.5X1X3 - 0.4X2X3 + 2.4X(1)(2) - 0.4X(2)(2) (R2 = 0.9). The equation shows that X1, X2 and X3 affected the release inversely, and the most significant interaction was between X1 and X2. Y5 has been maximized for optimization of naproxen release. CONCLUSIONS: Controlled release tablets of naproxen with predictable drug release characteristics were obtained by compressing its microspheres with Eudragit L100-55.