Studies on Formulation Development of Mucoadhesive Sustained Release Itraconazole Tablet Using Response Surface Methodology

The purpose of this research was to prepare and evaluate sustained release mucoadhesive tablets of Itraconazole. It is practically insoluble in aqueous fluids hence its solid dispersion with Eudragit E100 was prepared by spray drying. This was formulated in matrix of hydrophilic mucoadhesive polymers Carbopol 934P (CP) and Methocel K4M (HPMC). The formulation was optimized using a 3² factorial design. Amounts of CP and HPMC were taken as formulation variables for optimizing response variables i.e. mucoadhesion and dissolution parameters. The optimized mucoadhesive formulation was orally administered to albino rabbits, and blood samples collected were used to determine pharmacokinetic parameters. The solid dispersion markedly enhanced the dissolution rate of itraconazole. The bioadhesive strength of formulation was found to vary linearly with increasing amount of both polymers. Formulations exhibited drug release fitting Peppas model with value of n ranging from 0.61 to 1.18. Optimum combination of polymers was arrived at which provided adequate bioadhesive strength and fairly regulated release profile. The experimental and predicted results for optimum formulations were found to be in close agreement. The formulation showed C _max 1898 ± 75.23 ng/ml, t _max of the formulation was 2 h and AUC was observed to be 28604.9 ng h/ml     

Development and Evaluation of Sustained Release Gastroretentive Minimatrices for Effective Treatment of H. pylori Infection

In the present work, sustained release gastroretentive minimatrices of amoxicillin have been designed and optimized using central composite design. Effect of amount of xanthan gum, rate controlling polymers (HPMC K100M CR/PEO coagulant (1:1)), carbopol 974P, and gas generating couple (sodium bicarbonate/citric acid (3:1)) was studied on dependent (response) variables, i.e., buoyancy lag time, drug release at 1 h, time required for 95% drug release, swelling index, and bioadhesive strength. Minimatrices were prepared by non aqueous granulation method using solution of PVP K30 in isopropyl alcohol. All the formulations were found to contain 99.2% to 100.9% of amoxicillin per minimatrix. Optimum formulation (Formulation number AGT09) containing high level of the independent variables was having buoyancy lag time of 7 min and drug release at 1 h was 32.5%. It required 9.39 h for 95% drug release while swelling index and bioadhesive strength were 341 and 17.9 dyn/cm², respectively. This formulation was said to be optimum because it has minimum buoyancy lag time, requires maximum time for 95% drug release, and has higher bioadhesive capabilities. In vitro results of an optimized formulation indicate its sustained drug release and gastric retention capability, which may be very useful for effective treatment of H. pylori infection.     

Formulation optimization of chelerythrine loaded O-carboxymethylchitosan microspheres using response surface methodology

The aims of this investigation were to develop a procedure to prepare chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by emulsion cross-linking method and optimize the process and formulation variables using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio, O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The process and formulation variables were optimized to achieve maximum drug loading content and entrapment efficiency by the desirability function. The optimized microsphere formulation was characterized for particle size, shape, morphology and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency, and in vitro drug release of CHE-loaded O-CMCS microspheres were found to be of 12.18 μm, 4.16 ± 3.36%, 57.40 ± 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination use of RSM, BBD and desirability function could provide a promising application for O-CMCS as controlled drug delivery carrier and help to develop procedures for a lab-scale microemulsion process.     

Statistical optimization of gastric floating system for oral controlled delivery of calcium

The development of an optimized gastric floating drug delivery system is described. Statistical experimental design and data analysis using response surface methodology is also illustrated. A central, composite Box-Wilson design for the controlled release of calcium was used with 3 formulation variables: X₁ (hydroxypropyl methylcellulose [HPMC] loading), X₂ (citric acid loading), and X₃ (magnesium stearate loading). Twenty formulations were prepared, and dissolution studies and floating kinetics were performed on these formulations. The dissolution data obtained were then fitted to the Power Law, and floating profiles were analyzed. Diffusion exponents obtained by Power Law were used as targeted response variables, and the constraints were placed on other response variables. All 3 formulation variables were found to be significant for the release properties (P<,05), while only HPMC loading was found to be significant for floating properties. Optimization of the formulations was achieved by applying the constrained optimization. The optimized formulation delivered calcium at the release rate of 40 mg/hr, with predicted n and T_50% values at 0.93 and 3.29 hours, respectively. Experimentally, calcium was observed to release from the optimized formulation with n and T_50% values of 0.89 (±0.10) and 3.20 (±0.21) hours, which showed an excellent agreement. The quadratic mathematical model developed could be used to further predict formulations with desirable release and floating properties.     

Enhanced Bioavailability of Buspirone From Reservoir-Based Transdermal Therapeutic System,Optimization of Formulation Employing Box–Behnken Statistical Design

The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone (BUSP), a low bioavailable drug. A three-factor, three-level Box–Behnken design was employed to optimize the TTS. Hydroxypropyl methylcellulose, d-limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed a flux 104.6 μg cm⁻² h⁻¹, which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo–in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed and optimized using Box–Behnken statistical design and could provide an effective treatment in the management of anxiety.     

Optimization of a protective medium for enhancing the viability of freeze-dried Lactobacillus delbrueckii subsp. bulgaricus based on response surface methodology

Response surface methodology (RSM) was used to optimize a protective medium for enhancing the cell viability of Lactobacillus delbrueckii subsp. bulgaricus LB14 during freeze-drying. Using a previous Plackett–Burman design, it was found that sucrose, glycerol, sorbitol and skim milk were the most effective freeze-drying protective agents for L. bulgaricus LB14. A full factorial central composite design was applied to determine the optimum levels of these four protective agents. The experimental data allowed the development of an empirical model (P<0.0001) describing the inter-relationships between the independent and dependent variables. By solving the regression equation, and analyzing the response surface contour and surface plots, the optimal concentrations of the agents were determined as: sucrose 66.40 g/L, glycerol 101.20 g/L, sorbitol 113.00 g/L, and skim milk 130.00 g/L. L. bulgaricus LB14 freeze-dried in this medium obtained a cell viability of up to 86.53%.     

Optimization Studies on Gastroretentive Floating System Using Response Surface Methodology

The aim of the present investigation was to develop and optimize gastroretentive floating system of amoxicillin for the efficient treatment of peptic ulcer induced by Helicobacter pylori infection. Floating microballoons were developed using central composite design (CCD), and optimization was done by employing response surface methodology. The selected independent variables were cellulose acetate phthalate, drug–Eudragit S100 ratio, and the ratio of dichloromethane/ethanol/isopropyl alcohol. The selected dependent variables were yield, mean particle size, buoyancy, encapsulation efficiency, and drug release within 8 h. A quadratic polynomial model was generated which had linear, interaction, and quadratic terms to predict and evaluate the independent variables with respect to the dependent variables. Results showed that selected independent variables significantly affect the yield (30.53–82.71%), particle size (31.62–47.03 μm), buoyancy (42.68–95.75%), encapsulation efficiency (56.96–93.13%), and cumulative drug release from the microballoons (34.01–74.65%). The interaction and quadratic terms were also found to affect the process variables. An excellent agreement was found between the actual value and predicted value. In conclusion, it can be said that CCD is a valuable second-degree design to develop and optimize GFS of amoxicillin which in turn provides a basis to localize the drug release in the gastric region for effective treatment of H. pylori-mediated infection.     

Prolonged Intragastric Drug Delivery Mediated by Eudragit<Superscript>®</Superscript><Emphasis Type="Bold">E-Carrageenan Polyelectrolyte Matrix Tablets</Emphasis>

Interpolyelectrolyte (IPE) complexation between carrageenan (CG) and Eudragit E (EE) was studied in 0.1 M HCl and was used to develop floating matrix tablets aimed to prolong gastric-residence time and sustain delivery of the loaded drug. The optimum EE/CG IPE complexation weight ratio (0.6) was determined in 0.1 M HCl using apparent viscosity measurements. The IPE complex was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Metronidazole matrix tablets were prepared by direct compression using EE, CG, or hybrid EE/CG with ratio optimal for IPE complexation. Corresponding effervescent tablets were prepared by including Na bicarbonate as an effervescent agent. Tablets were evaluated for in vitro buoyancy and drug release in 0.1 M HCl. Both CG and EE–CG effervescent matrices (1:2 drug to polymer weight ratio, 60 mg Na bicarbonate) achieved fast and prolonged floating with floating lag times less than 30 s and floating duration of more than 10 h. The corresponding EE effervescent matrices showed delayed floating and rapid drug release, and completely dissolved after 3 h of dissolution. CG matrices showed an initial burst drug release (48.3 ± 5.0% at 1 h) followed by slow drug release over 8 h. EE–CG matrices exhibited sustained drug release in almost zero-order manner for 10 h (68.2 ± 6.6%). The dissolution data of these matrices were fitted to different dissolution models. It was found that drug release followed zero-order kinetics and was controlled by the superposition of the diffusion and erosion.     

Terminalia Gum as a Directly Compressible Excipient for Controlled Drug Delivery

The exudates from the incised trunk of Terminalia randii has been evaluated as controlled release excipient in comparison with xanthan gum and hydroxypropylmethylcellulose (HPMC) using carvedilol (water insoluble) and theophylline (water soluble) as model drugs. Matrix tablets were prepared by direct compression and the effects of polymer concentration and excipients—spray dried lactose, microcrystalline cellulose and dicalcium phosphate dihydrate on the mechanical (crushing strength (CS) friability (F) and crushing strength–friability ratio (CSFR)) and drug release properties of the matrix tablets were evaluated. The drug release data were fitted into different release kinetics equations to determine the drug release mechanism(s) from the matrix tablets. The results showed that the CS and CSFR increased with increase in polymer concentration while F decreased. The ranking of CS and CSFR was HPMC > terminalia > xanthan while the ranking was reverse for F. The ranking for t ₂₅ (i.e. time for 25% drug release) at a polymer concentration of 60% was xanthan > terminalia = HPMC. The dissolution time, t ₂₅, of theophylline matrices was significantly lower (p < 0.001) than those of carvedilol matrix tablets. Drug release from the matrices was by swelling, diffusion and erosion. The mechanical and drug release properties of the tablets were significantly (p < 0.05) dependent on the type and concentration of polymer and excipients used with the release mechanisms varying from Fickian to anomalous. Terminalia gum compared favourably with standard polymers when used in controlled release matrices and could serve as a suitable alternative to the standard polymers in drug delivery.     

Solubility-modulated asymmetric membrane tablets of triprolidine hydrochloride: statistical optimization and evaluation

The aim of the present study was to develop asymmetric membrane (AM) tablets for controlled delivery of highly water-soluble antihistaminic drug triprolidine hydrochloride. The solubility of triprolidine hydrochloride was modulated through the incorporation of coated sodium chloride crystals encapsulated with asymmetric membrane coating polymer, cellulose acetate butyrate. Formulation of AM tablets was based on a 2³ factorial design to study the effect of formulation variables, namely, polymer concentration, level of pore former, and amount of osmogen on the in vitro release. Core tablets prepared by wet granulation and coated with asymmetric membrane by a dip coating method were evaluated. Statistical analysis was done with the Design Expert Software 8.0.2 (USA), and the polynomial equation generated by Pareto charts was used for validation of the experimental design. The interaction chart and response surface plots deduced the simultaneous effect of independent variables on in vitro drug release. The in vitro drug release was inversely proportional and directly related to the level(s) of polymer and pore former in the membrane, respectively. The level of osmogen not only increased the osmotic pressure but also controlled the drug release due to a common ion effect. The drug release of the optimized formulation (F6) followed zero-order kinetics, which would be capable of reducing the administration, and was stable over 3 months. SEM photographs revealed asymmetry in membrane structure.     

Optimization on conditions of podophyllotoxin-loaded liposomes using response surface methodology and its activity on PC3 cells

The purpose of this study was to optimize the preparation conditions of podophyllotoxin liposomes (PPT-Lips), and to investigate their effects on PC3 cells. PPT-Lips were prepared by using a thin-film dispersion method. In order to achieve maximum drug encapsulation efficiency (EE), the process and formulation variables were optimized by response surface methodology (RSM). The optimum preparation conditions were cholesterol to lecithin ratio of 3.6:40 (w/w), lipid to drug ratio of 15.8:1 (w/w), and the ultrasonic intensity of 35% (total power of 400?W). The experimental EE of PPT-Lips was 90.425%, which was consistent with the theoretically predicted value. The characterization studies showed that PPT-Lips were well-dispersible spherical particles with an average size of 106?nm and a zeta potential of –10.1?mV. A gradual and time-dependent pattern of PPT from liposomes was found in in vitro drug release with a cumulative release amount up to 70.3% in 24?h. Results of cell viability experiments on PC3 cells demonstrated that PPT-Lips exhibited more effective anticancer activity in comparison with free PPT. Therefore, PPT-Lips represent an efficient and promising drug delivery system for PPT.     

Statistical analysis of inactivation of Listeria monocytogenes subjected to high hydrostatic pressure and heat in milk buffer

Previous unpublished experimental results of fractional factorial experiments showed that significant external factors affecting high-pressure processing (HPP) inactivation were pressure, temperature, and pressure holding time. Based on these results, response surface methodology (RSM) was employed in the present work, and a quadratic equation for HPP inactivation was built with RSM. By analyzing response surface plots and their corresponding contour plots and by solving the quadratic equation, experimental values were shown to be significantly in good agreement with predicted values, since the adjusted determination coefficient (R _Adj ²) was 0.9812 and the level of significance was P<0.0001. Optimum process parameters for a 6-log cycle reduction of Listeria monocytogenes were obtained: pressure, 448.0 MPa; temperature, 41°C; and pressure holding time, 11 min. The adequacy of the model equation in predicting optimum response values was verified effectively by validation data.     

Development of tea tree oil-loaded liposomal formulation using response surface methodology

Abstract

The aim of this study is to prepare tea tree oil liposome (TTOL) and optimize the preparation condition by single factor experiment and statistical design. TTOL was prepared using a thin-film hydration with the combination of sonication method and the preparation conditions of TTOL were optimized with response surface methodology (RSM). The optimal preparation conditions for TTOL by response surface methodology were as follows: the mass ratio of PC and Cho 5.51, TTO concentration 1.21% (v/v) and Tween 80 concentration 0.79% (v/v). The response surface analysis showed that the significant (p?<?0.05) second-order polynomial regression equations successfully fitted for all dependent variables with no significant (p?>?0.05) lack of fit for the reduced models. Furthermore, the interaction of the mass ratio of PC/Cho and TTO concentration had a significant effect. The amounts of Tween 80 required were also reduced with RSM. Under these conditions, the experimental encapsulation efficiency of TTOL was 97.81?±?0.33%, which was close with the predicted value. Therefore, the optimized preparation condition was very reliable. The increased entrapment efficiency would significantly improve the TTO stability and bioavailability.     

Mucoadhesive bilayer tablets of propranolol hydrochloride

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration. Published: September 21, 2007     

Once-daily tablet formulation and in vitro release evaluation of cefpodoxime using hydroxypropyl methylcellulose: A technical note

Summary and Conclusions  Decreasing the dose frequency of cefpodoxime proxetil increases patient compliance; patients prefer to take the drug once daily. It also improves the rate of bacterial killing and hastens the cure from the indications, and therefore increases compliance. The hydrophilic matrix of HPMC controlled the cefpodoxime proxetil release effectively for 24 hours; hence, the formulation can be considered as a once-daily sustained-release tablet of cefpodoxime proxetil. The formulation showed acceptable pharmacotechnical properties and assay requirements. In vitro dissolution studies indicated a sustained-release pattern throughout 24 hours of the study that was comparable to the theoretical release profile. Drug release kinetics indicated that drug release was best explained by Higuchi’s equation, as these plots showed the highest linearity (r ²=0.9734), but a close relationship was also noted with zero-order kinetics (r ²=0.9708). Korsmeyer’s plots indicated ann value of 0.57, which was indicative of an anomalous diffusion mechanism or diffusion coupled with erosion; hence, the drug release was controlled by more than one process. Hixson-Crowell plots indicated a change in surface area and diameter of the tablets with the progressive dissolution of the matrix as a function of time. Published: September 22, 2006     

In Situ Forming Formulation: Development, Evaluation, and Optimization Using 33 Factorial Design

The present investigation concerns with the development and optimization of an in situ forming formulation using 3³ full factorial design experimentation. Metformin, an antidiabetic drug with upper part of gastrointestinal tract as absorption window was used as a model drug. The formulations were designed with an objective to retain in stomach for an extended time period. The effect of three independent factors—concentrations of sodium alginate (X ₁), gellan gum (X ₂), and metformin (X ₃) on in vitro drug release were used to characterize and optimize the formulation. Five dependent variables—release exponent (Y ₁), dissolution efficiency (Y ₂), drug release at 30 min (Y ₃), 210 min (Y ₄), and 480 min (Y ₅) were considered as optimization factors. The data were statistically analyzed using ANOVA, and a p < 0.05 was considered statistically significant. Three dimensional surface response plots were drawn to evaluate the interaction of independent variables on the chosen dependent variables. Of the prepared 27 formulations, the responses exhibited by batch F17 containing medium level sodium alginate (X ₁), low level gellan (X ₂), and medium level metformin (X ₃) were similar to the predicted responses.     

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation

Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6?±?3.28, 54.4?±?4.26, 56.1?±?7.48 and 46.0?±?2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16?±?4.22, 24.81?±?5.35, 8.17?±?1.81 and 8.92?±?3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.     

Investigation of the Physicochemical and Physicomechanical Properties of a Novel Intravaginal Bioadhesive Polymeric Device in the Pig Model

The purpose of this study was to develop and evaluate the bioadhesivity, in vitro drug release, and permeation of an intravaginal bioadhesive polymeric device (IBPD) loaded with 3′-azido-3′-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Modified polyamide 6,10, poly(lactic-coglycolic acid), polyacrylic acid, polyvinyl alcohol, and ethylcellulose were blended with model drugs AZT and PSS as well as radio-opaque barium sulfate (BaSO4) and then compressed into caplet devices on a tableting press. One set of devices was coated with 2% w/v pentaerythritol polyacrylic acid (APE-PAA) while another remained uncoated. Thermal analysis was performed on the constituent polymers as well the IBPD. The changes in micro-environmental pH within the simulated human vaginal fluid due to the presence of the IBPD were assessed over a period of 30 days. Textural profile analysis indicated that the bioadhesivity of the APE-PAA-coated devices (3.699 ± 0.464 N; 0.0098 ± 0.0004 J) was higher than that of the uncoated devices (1.198 ± 0.150 N; 0.0019 ± 0.0001 J). In addition, BaSO4-facilitated X-ray imaging revealed that the IBPD adhered to pig vaginal tissue over the experimental period of 30 days. Controlled drug release kinetics was obtained over 72 days. During a 24-h permeation study, an increase in drug flux for both AZT (0.84 mg cm⁻² h⁻¹) and PSS (0.72 mg cm⁻² h⁻¹) was realized up to 12 h and thereafter a steady-state was achieved. The diffusion and dissolution dynamics were mechanistically deduced based on a chemometric and molecular structure modeling approach. Overall, results suggested that the IBPD may be sufficiently bioadhesive with desirable physicochemical and physicomechanical stability for use as a prolonged intravaginal drug delivery device.     

Statistical Design for Formulation Optimization of Hydrocortisone Butyrate-Loaded PLGA Nanoparticles

The aim of this investigation was to develop hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) with ideal encapsulation efficiency (EE), particle size, and drug loading (DL) under emulsion solvent evaporation technique utilizing various experimental statistical design modules. Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett–Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process leads to an optimum formulation with desired EE, particle size, and DL. Contour plots and response surface curves display visual diagrammatic relationships between the experimental responses and input variables. The concentration of PLGA, drug, and polyvinyl alcohol and sonication time were the critical factors influencing the responses analyzed. Optimized formulation showed EE of 90.6%, particle size of 164.3 nm, and DL of 64.35%. This study demonstrates that statistical experimental design methodology can optimize the formulation and process variables to achieve favorable responses for HB-loaded NP.     

Development and Statistical Optimization of Solid Lipid Nanoparticles of Simvastatin by Using 2<Superscript>3</Superscript> Full-Factorial Design

The objective of this study was to develop solid lipid nanoparticles (SLNs) of simvastatin and to optimize it for independent variables (amount of glycerol monostearate, concentration of poloxamer, and volume of isopropyl alcohol) in order to achieve desired particle size with maximum percent entrapment efficiency (% EE) and percent cumulative drug release (% CDR). To achieve our goal, eight formulations (F ₁–F ₈) of SLNs were prepared by solvent injection technique and optimized by 2³ full-factorial design. The design was validated by extra design checkpoint formulation (F ₉), and the possible interactions between independent variables were studied. The responses of the design were analyzed using Design Expert 7.1.6. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw Pareto charts and response surface plots. On the basis of software analysis, formulation F ₁₀ with a desirability factor of 0.611 was selected as optimized formulation and was evaluated for the independent parameters. Optimized formulation showed particle size of 258.5 nm, % EE of 75.81%, with of 82.67% CDR after 55 h. The release kinetics of the optimized formulation best fitted the Higuchi model, and the recrystallization index of optimized formulation was found to be 65.51%.