Formulation optimization of transdermal meloxicam potassium-loaded mesomorphic phases containing ethanol,oleic acid and mixture surfactant using the statistical experimental design methodology

Response surface methodology (RSM) was used to develop and optimize the mesomorphic phase formulation for a meloxicam transdermal dosage form. A mixture design was applied to prepare formulations which consisted of three independent variables including oleic acid (X₁), distilled water (X₂) and ethanol (X₃). The flux and lag time (LT) were selected as dependent variables. The result showed that using mesomorphic phases as vehicles can significantly increase flux and shorten LT of drug. The analysis of variance showed that the permeation parameters of meloxicam from formulations were significantly influenced by the independent variables and their interactions. The X₃ (ethanol) had the greatest potential influence on the flux and LT, followed by X₁ and X₂. A new formulation was prepared according to the independent levels provided by RSM. The observed responses were in close agreement with the predicted values, demonstrating that RSM could be successfully used to optimize mesomorphic phase formulations.     

Formulation optimization of meloxicam sodium gel using response surface methodology

The influences of a combination of different mechanisms of penetration enhancers on the penetration absorption properties of meloxicam sodium formulations through rat skin were investigated using response surface methodology. A uniform design was applied to prepare model formulations systematically that were composed of four independent variables: the content of ethanol (x(1)), propylene glycol (x(2)), menthol (x(3)), and azone (x(4)). The penetration rate (flux) of meloxicam sodium gel through rat skin was chosen as the response which had to be higher than 400microg/hcm(2) the required flux of meloxicam gel to maintain a therapeutic concentration. The result showed optimal formulation could be obtained from this response surface methodology. Menthol had the greatest potential influence on the penetration absorption of meloxicam sodium, followed by azone, ethanol and PG, respectively. By in vivo study, meloxicam could be determined 1h after topical administration and reached steady-state concentration at about 12h. The bioavailability (%) of the optimal meloxicam sodium gel was about 50.1%.     

Development and optimization of a novel oral controlled delivery system for tamsulosin hydrochloride using response surface methodology

The purpose of this study was to develop and optimize oral controlled-release formulations for tamsulosin hydrochloride using a combination of two cellulose ester derivatives, hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose phthalate (HPMCP), with Surelease as a coating material. A three-factor, three-level Box-Behnken design was used to prepare systematic model formulations, which were composed of three formulation variables, the content of HPMC (X(1)) and HPMCP (X(2)) and the coating level (X(3)), as independent variables. The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal coating formulation with a specific release rate at different time intervals. The drug release percentages at 2, 3 and 5h were the target responses and were restricted to 15-30% (Y(1)), 50-65% (Y(2)) and 80-95% (Y(3)), respectively. The optimal coating formulation was achieved with 10% HPMC and 20% HPMCP at a coating level of 25%, and the observed responses coincided well with the predicted values from the RSM optimization technique. The drug release from pellets coated with the optimized formulation showed a controlled-release pattern (zero-order), in comparison with a commercial product (Harunal capsule). In conclusion, a novel, oral, controlled-release delivery system for tamsulosin hydrochloride was successfully developed by incorporating HPMC and HPMCP as coating additives into Surelease aqueous ethylcellulose dispersion.     

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.     

Formulation Optimization of Estradiol Microemulsion Using Response Surface Methodology

The aim of the current study was to find an optimal estradiol-loaded microemulsion with higher permeation rate and shortened lag time (LT) for transdermal application by using a response surface methodology (RSM) and constrained mixture design. Isopropyl myristate (X₁), distilled water (X₂), and ethanol (X₃) were selected as independent variables, whereas the viscosity of microemulsion and permeation parameters including the cumulative amount at 24 h (Q_24h) and LT of estradiol-loaded microemulsion through skin were set as dependent variables. The result showedthat the three independent variables had a remarkable effect (p < 0.05) on the dependent variables. Moreover, the predicted and observed values of these three dependent variables of the optimal microemulsion formulations, which were produced by the RSM optimization technique, were close, demonstrating that RSM was a useful technique for optimizing pharmaceutical formulations. However, the experimental estradiol-loaded microemulsion with higher permeation rate was expected to provide effective therapeutic concentration in a workable administration area. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4383–4389, 2011     

Optimization of pH-independent release of nicardipine hydrochloride extended-release matrix tablets using response surface methodology

The purpose of this study was to optimize the pH-dependent release of nicardipine hydrochloride extended release formulations by using simultaneously combination two hydrophilic polymers: hydroxypropylmethylcellulose (HPMC) and sodium alginate as retardant and avicel as additive. The constrained mixture experimental design was used to prepare systematic model formulations which were composed of three formulation variables: the content of HPMC (X1), avicel (X2), and sodium alginate (X3). The response surface methodology (RSM) and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals and to quantify the effect of each formulation variables. The drug release percent at 3, 6 and 12 h were the target responses and were restricted to 10-30% (Y3h), 40-65% (Y6h) and not less than 80% (Y12h), respectively. The results showed that the effect of combination of HPMC and sodium alginate was the most influence factor on the drug release from extended-release matrix tablets. The observed results of Y3h, Y6h and Y12h coincided well with the predictions in the RSM optimization technique, indicating it was quite useful for optimizing pharmaceutical formulation. The mechanism of drug release from extended-release matrix tablets was dependent on the added amount of alginate. The release kinetic of drug from HPMC matrix tablets with alginate was followed the zero-order release pattern.     

星点设计-效应面法优化硝酸布康唑缓释乳膏的制备

目的 采用星点设计-效应面法对硝酸布康唑缓释乳膏的处方进行优化。方法 以液体石蜡用量(X₁)、乳化剂用量(X₂)、助乳化剂占乳化剂比例(X₃)为考察因素,以24,48,72 h的累积释放度为考察指标,分别用多元线性模型、二次多项式模型描述考察指标和3个考察因素之间的数学关系,根据模型绘制效应面图和等高线图,通过重叠等高线图确定优化处方,最后进行验证。结果 二次多项式模型比多元线性模型置信度高;根据二次多项式模型,发现 3 个考察因素和 3个考察指标之间存在可信的定量关系;优化处方各设定指标的预测值和实际值非常接近。结论 星点设计-效应面法可用于硝酸布康唑缓释乳膏的处方优化,所建模型具有良好的预测能力。     

Formulation development of ambroxol hydrochloride soft gel with application of statistical experimental design and response surface methodology

The purpose of present work was to develop ambroxol hydrochloride soft gel formulation with the application of statistical experimental design and response surface methodology (RSM). A two-factor, three-level (3(2)) full factorial design of experiment with RSM was run to evaluate the main and interaction effect of two independent formulation variables that included the amount of low-acetylated gellan gum and sodium citrate. The dependent variables included viscosity (Y(1)), amount of drug release at 10 min (Y(2)) and 30 min (Y(3)), and gelation time (Y(4)). In order to obtain a formulation having the maximum amount of drug release at 10 min and minimum gelation time, RSM optimization was used. The prepared formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. All the formulations showed a gelation time in the range of 6 to 48 min. The drug content in all the formulations was within limit (99.6 ± 1.56%). The viscosity of all the formulations was found in the range of 1872-12,182 cP. Dissolution studies of the formulations showed drug release in the range of 40.56-72.46% within 10 min and 80.2-100.5% within 30 min. Human evaluation tests revealed that all the gels possessed acceptable characteristics. This study showed that the soft gel formulation GA5, containing 0.3% of gellan gum and 0.4% of sodium citrate, has potential use as an immediate release soft gel for oral drug delivery. LAY ABSTRACT: The objective of this investigation was to develop a new, immediate-release, soft gel dosage form for ambroxol hydrochloride, an oral expectorant and mucolytic agent. This novel soft gel dosage form needs to be suitable for pediatric and geriatric patients as well as patients with dysphagia. A statistical technique was used for optimization of the gel formulation. The methodology, called a design of experiment with response surface methodology, evaluated several independent formulation variables, including the amount of two ingredients, low-acetylated gellan gum and sodium citrate. Their effects were studied by comparing physical properties of the gel such as viscosity, amount of drug release at 10 and 30 min, and gelation time. The final optimized formulation (0.3% of gellan gum and 0.4% of sodium citrate) was chosen to maximize the amount of drug release at 10 min, minimize gelation time, and optimize viscosity in a reasonable range. After this optimization exercise, the prepared ambroxol hydrochloride soft gel formulations were evaluated for pH, viscosity, rheological properties, gelation time, drug content, in vitro drug release, appearance, and taste. Human evaluation tests revealed that all the gels possessed acceptable organoleptic characteristics.     

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.     

Application of a mixture experimental design in the optimization of a self-emulsifying formulation with a high drug load

Response surface methodology (RSM) was applied to optimize the self-emulsifying drug delivery system (SEDDS) containing 25% (w/w) Drug A, a model drug with a high lipophilicity and low water solubility. The key objective of this study was to identify an optimal SEDDS formulation that: 1) possesses a minimum concentration of the surfactant and a maximum concentration of lipid and 2) generates a fine emulsion and eliminates large size droplets (> or = 1 microm) upon dilution with an aqueous medium. Three ingredient variables [PEG 400, Cremophor EL, and a mixture of glycerol dioleate (GDO), and glycerol monooleate (GMO)] were included in the experimental design, while keeping the other ingredients at a fixed level (25% Drug A, 6% ethanol, 3% propylene glycol, 4% water, and 2% tromethamine) in the SEDDS formulation. Dispersion performance of these formulations upon dilution with a simulated gastrointestinal fluid was measured, and the population of the large droplets was used as the primary response for statistical modeling. The results of this mixture study revealed significant interactions among the three ingredients, and their individual levels in the formulation collectively dictated the dispersion performance. The fitted response surface model predicted an optimal region of the SEDDS formulation compositions that generate fine emulsions and essentially eliminates large droplets upon dilution. The predicted optimal 25% Drug A-SEDDS formulations with the levels of Cremophor EL ranging from 40-44%, GDO/GMO ranging from 10-13%, and PEG 400 ranging from 2.7-9.0% were selected and prepared. The dispersion experiment results confirmed the prediction of this model and identified potential optimal formulations for further development. This work demonstrates that RSM is an efficient approach for optimization of the SEDDS formulation.     

Optimizing the novel formulation of liposome-polycation-dna complexes (lpd) by central composite design

LPD vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA and liposomes. Here, we described a novel anionic LPD formulation containing protamine-DNA complexes and pH sensitive liposomes composed of DOPE and cholesteryl hemisuccinate (Chems). Central composite design (CCD) was employed to optimize stable LPD formulation with small particle size. A three factor, five-level CCD design was used for the optimization procedure, with the weight ratio of protamine/DNA (X1), the weight ratio of Chems/ DNA (X2) and the molar ratio of Chems/DOPE in the anionic liposomes (X3) as the independent variables. LPD size (Y1) and LPD protection efficiency against nuclease (Y2) were response variables. Zeta potential determination was utilized to define the experimental design region. Based on experimental design, 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 optimized X1-X3 levels that achieve the desired particle size and the protection efficiency against nuclease. According to these levels, an optimized LPD formulation was prepared, resulting in a particle size of 185.3 nm and protection efficiency of 80.22%.     

Application of a Mixture Experimental Design in the Optimization of a Self‐Emulsifying Formulation with a High Drug Load

Response surface methodology (RSM) was applied to optimize the self‐emulsifying drug delivery system (SEDDS) containing 25% (w/w) Drug A, a model drug with a high lipophilicity and low water solubility. The key objective of this study was to identify an optimal SEDDS formulation that: 1) possesses a minimum concentration of the surfactant and a maximum concentration of lipid and 2) generates a fine emulsion and eliminates large size droplets (≥ 1 µm) upon dilution with an aqueous medium. Three ingredient variables [PEG 400, Cremophor EL, and a mixture of glycerol dioleate (GDO), and glycerol monooleate (GMO)] were included in the experimental design, while keeping the other ingredients at a fixed level (25% Drug A, 6% ethanol, 3% propylene glycol, 4% water, and 2% tromethamine) in the SEDDS formulation. Dispersion performance of these formulations upon dilution with a simulated gastrointestinal fluid was measured, and the population of the large droplets was used as the primary response for statistical modeling. The results of this mixture study revealed significant interactions among the three ingredients, and their individual levels in the formulation collectively dictated the dispersion performance. The fitted response surface model predicted an optimal region of the SEDDS formulation compositions that generate fine emulsions and essentially eliminates large droplets upon dilution. The predicted optimal 25% Drug A–SEDDS formulations with the levels of Cremophor EL ranging from 40–44%, GDO/GMO ranging from 10–13%, and PEG 400 ranging from 2.7–9.0% were selected and prepared. The dispersion experiment results confirmed the prediction of this model and identified potential optimal formulations for further development. This work demonstrates that RSM is an efficient approach for optimization of the SEDDS formulation.     

Formulation design of microemulsion for dermal delivery of penciclovir

The purpose of the present study was to evaluate the potential application of microemulsions as a dermal drug delivery loading penciclovir. The pseudo-ternary phase diagrams were developed for various microemulsion formulations composed of oleic acid (oil phase), Cremorphor EL (surfactant) and ethanol (cosurfactant). Composition of microemulsion systems was optimized using simplex lattice mixture design including the concentrations of surfactant, cosurfactant and water (independent variables) and the solubility and the cumulative amount of penciclovir permeated through excised mouse skins per unit area (response variables). The physicochemical properties of the optimized microemulsion and the permeating ability of penciclovir from microemulsions were also investigated. The results showed that the optimized microemusion formulation was composed of oleic acid (5%, w/w), Cremorphor EL (20%, w/w), ethanol (30%, w/w) and water (45%, w/w). The mean particle diameter was 36.5nm and solubility of penciclovir in the emulsion was 7.41 mg g(-1). The cumulative amount of penciclovir permeated through excised mouse skins from microemulsion was about 3.5 times that of the commercial cream. The conclusion was that the permeating ability of penciclovir was significantly increased from the microemulsion formulation compared with commercial cream.     

Process optimization by response surface design and characterization study on geniposide pharmacosomes

The objective of this study was to prepare and characterize geniposide-pharmcosomes (GP-PMS) and optimize the process and formulation variables using response surface methodology. Tetrahydrofuran was used as a reaction medium, GP and phospholipids were resolved into the medium, and GP-PMS was formed after the organic solvent was evaporated off under vacuum condition. The process and formulation variables were optimized by central composite design (CCD) of response surface methodology (RSM). The phospholipid-to-drug ratio (X(1)), reaction temperature (X(2)) and the drug concentration (X(3)) were selected as independent variables and the yield (%) of GP 'present as a complex' in the PMS was used as the dependent variable. The physico-chemical properties of the complex obtained by optimal parameters were investigated by means of Fourier transform infrared spectrophotometry (FT-IR), differential scanning calorimetry, n-octanol/water partition coefficient (P) and particle size analysis. Multiple linear regression analysis for optimization by CCD revealed that the higher the yield of GP 'present as a complex' in the GP-PMS was obtained wherein the optimal settings of X(1), X(2) and X(3) are 3, 50°C and 5.5?mg/mL, respectively. The DSC and IR studies of GP-PMS by the optimal settings demonstrated that GP and phospholipids in the GP-PMS were combined by non-covalent bond, not forming a new compound. GP-PMS could significantly increased the lipophilicify of GP, and P of GP-PMS in n-octanol and water was about 20 multiples more than that of GP material. Pharmacosomes could be an alternative approach to improve the absorption and permeation of biologically active constituents.     

Optimization and characterization of controlled release multi-particulate beads formulated with a customized cellulose acetate butyrate dispersion

The objectives of the present investigation were: (1) to model the effect of process and formulation variables viz., coating weight gain, duration of curing, and plasticizer concentration on in-vitro release profile of verapamil HCl from multi-particulate beads formulated with a novel aqueous-based pseudolatex dispersion; (2) to optimize the formulation by response surface methodology (RSM) and artificial neural network (ANN); and (3) to characterize the optimized product by thermal and X-ray analyses. Inert beads (Nupareil) were loaded with verapamil HCl and subsequently coated with a custom designed aqueous-based pseudolatex dispersion of cellulose acetate butyrate (CAB). Experiments were designed and data was collected according to a three factor, three level face centered central composite design. Data was analyzed for modeling and optimizing the release profile using both RSM and ANN. Model fitted the data and explained 90% of variability in response in the case of RSM and at least 70% in the case of ANN. Release profile was optimized for a zero-order model. Optimized formulations were prepared according to the factor combinations dictated by RSM and ANN. In each case, the observed drug release data of the optimized formulations was close to the predicted release pattern. However, the modeling and optimization abilities of RSM as evaluated by the R-squared values, were found to be higher than that of ANN. X-ray and drug content analysis suggested the absence of any degradation of verapamil HCl and excipients incorporated in the formulation.     

Optimization study on the formulation of roxithromycin dispersible tablet using experimental design

This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1*X2> X2*X2> X2*X3> X3*X3> X1*X3> X1*X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.     

星点设计-效应面法优化葫芦素口服脂质纳米乳剂的处方

目的借助星点设计-效应面法确定葫芦素口服脂质纳米乳剂的最优处方。方法提出了2个量化乳剂稳定性的常数:灭菌稳定性常数KS和冻融稳定性常数KF。用微射流仪制备葫芦素口服脂质纳米乳剂,采用星点设计-效应面法,以葫芦素口服脂质纳米乳剂的平均粒径(Y1)、灭菌稳定性常数KS(Y2)及冻融稳定性常数KF(Y3)为评价指标,考察了葫芦素口服脂质纳米乳剂处方中聚氧乙烯40氢化蓖麻油的用量(X1)、大豆卵磷脂的用量(X2)及中链脂肪酸甘油三酯的用量(X3)对制剂的影响,以效应面法预测最佳处方。结果优选的最优处方为:m(聚氧乙烯40氢化蓖麻油)∶m(大豆卵磷脂)∶m(中链脂肪酸甘油三酯)=1.15∶0.50∶5.52。采用优化处方制得的葫芦素口服脂质纳米乳剂的平均粒径为(113.6±2.1)nm,灭菌稳定性常数KS为2.92±0.7,冻融稳定性常数KF为5.14±0.2,同预测值的偏差均较低,最大偏差为4.6%。结论星点设计-效应面法所建立的模型能较好地应用于葫芦素口服脂质纳米乳剂处方的优化。     

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.     

Formulation and Optimization of Clotrimazole-Loaded Proniosomal Gel Using 32 Factorial Design

The main aim of the study was to develop and statistically optimize the proniosomal gel for enhanced transdermal delivery using 3² factorial designs to investigate the influence of both non-ionic surfactant and cholesterol to maximize the entrapment efficiency and flux. The concentration of non-ionic surfactant and cholesterol were taken as independent variables, while entrapment efficiency and flux were taken as dependent variables. The study showed that the entrapment efficiency depends on both cholesterol and surfactant, whereas permeation flux depends only on the surfactant. Proniosomal gel showed a significantly enhanced drug permeation through the skin, with an enhancement ratio 3.81±1.85 when compared to the drug solution. Comparative evaluation of permeation studies and the in vitro release study of optimized proniosomal gel (F5) with that of marketed gel and carbopol gel showed that the penetration of the optimized formulation was enhanced 1.75 times in comparison with that of the marketed formulation, and the release was in a controlled manner. Similarly, the anticandidial activity showed a significantly higher activity (p<0.05) than the marketed and carbopol gel. This may be due to the enhanced penetration of noisome-containing drug through the fungal cell wall, inhibiting the ergo sterol synthesis, thereby causing the fungal cell death due to the presence of penetration enhancer. The stability study at two different temperatures (30 ± 2°C and 4 ± 2°C) confirmed that the formulations were stable even at the end of 45 days. Hence, proniosomal gel is an efficient carrier for the delivery of clotrimazole, thereby prolonging the action.     

Effect of different formulation variables on some particle characteristics of poly (DL-lactide-co-glycolide) nanoparticles

This study investigates the effect of some formulation variables on particulate characteristics of poly (DL-lactide-co-glycolide) (PLGA) copolymer nanoparticles by applying 2(3) factorial design and response surface methodology (RSM). Nanoparticles were prepared by solvent displacement technique. Initially, appropriate formulation factors for elaboration of polymeric particles were selected by screening. A 2(3) full factorial design was employed to evaluate the influence of three formulation variables, polymer concentration (X(1)), dispersant concentration (X(2)) and phase volume ratio (X(3)) on the percentage of total particles at submicron range (Y(1)), mean diameter (Y(2)) and specific surface area (Y(3)) as particle characteristics. The results showed that all the three variables had significant influence on mean diameter of particles and amount of particles at submicron range. Simultaneous change of polymer concentration and dispersant concentration had significant effect on specific surface area of particles. Span value as an index of polydispersity indicated uniformity in particle size distribution.