Optimization of Composition and Process for Preparing Metaxalone Nanosuspension using Factorial Design

Author(s):  
Lakshmi Gubbala ◽  
Srinivas Arutla ◽  
Vobalaboina Venkateshwarlu

In the current study, the composition and process for preparing the nanosuspension of metaxalone (MX) has been optimized by using design of experiments (DOE). MX is skeletal muscle relaxant and belongs to BCS class II1 , the class wherein invivo drug dissolution is a rate-limiting step for drug absorption2 . High pressure homogenization (HPH) method was used to prepare the nanosuspension and Hydroxy propyl methyl cellulose (HPMC) and sodium lauryl sulfate (SLS) as surface stabilizers. For optimization studies three square (32 ) factorial design was used. For the composition optimization, concentration of the stabilizers and for process optimization homogenization time and pressure are used as independent variables. The dependent variables were particle size (PS), polydispersity index (PDI), zeta potential (ZP). The relationship between the dependent and independent variables was studied by response surface plots and contour plots. From the data it has been observed that 2.5 % HPMC, 0.5 % SLS were optimum concentrations and 1000 bar pressure, 120 minutes of homogenization were optimum process conditions producing least PS, PDI and high zeta potential. The optimized nano composition prepared by using optimum process conditions was observed to release more than 80 % within 30 minutes and found to be stable after 3 months of storage at room temperature. The solid state characterization (XRD, DSC) data of spray dried nanoparticles of the optimized composition has shown retention of drug crystallinity. IR has shown drug is compatible with the excipients used. SEM photograph has shown spherical drug nanoparticles. The optimization studies by applying the DOE resulted in considerable decrease in the experimentation work to achieve the stable nanosuspension with desired parameters such as PS, PDI and ZP.

2018 ◽  
Vol 19 (1) ◽  
pp. 15-23 ◽  
Author(s):  
MOHAMMED SAEDI JAMI ◽  
MAIZIRWAN MEL ◽  
AYSHA RALLIYA MOHD ARIFF ◽  
Qabas Marwan Abdulazeez

Sludge treatment is one of the most important and expensive steps in water and wastewater treatment plants. Chemical conditioners such as polyaluminum chloride, aluminum sulfate, Fenton’s reagent, gypsum, and polyacrylamide can produce byproducts that cause health and environmental problems. Moringa oleifera (MO) seeds can be used as a natural alternative to chemical conditioners. The bioactive materials have to be extracted from MO seeds for better performance. In this study, the treatment methods of MO seeds were the bioactive extraction by NaCl (1 M) and oil extraction by hexane solvent, as well as the untreated (crude) seeds powder. Synthetic sludge samples were prepared using kaolin suspension (5% w/v). The most effective coagulant-form was determined based on the values of settling velocity (Vs) and sludge volume index (SVI). Results showed that extraction by NaCl gave the best results of 0.41 cm/min of settling velocity and 63.39 ml/g of SVI. A SVI value greater than 150 ml/g indicates poor settling qualities whereas the control sludge of the current study was 100 ml/g. The most effective coagulant-form was optimized with respect to three process conditions: MO seeds dosage, mixing speed, and contact time. The experiments were designed using 2 Level Factorial-Design by Design-Expert software. The optimum process conditions were seeds dosage of 3246 mg/l, mixing speed of 102 rpm, and mixing time of 29 min. MO seeds can be considered as a natural coagulant that can be used as main sludge conditioner. ABSTRAK: Rawatan kotoran mendapan adalah salah satu rawatan penting dan termahal dalam merawat air dan sisa­ kumbahan loji. Perapi kimia seperti poli-aluminium klorida, aluminium sulfida, reagen Fenton, gipsum, dan poli-akrilamida menghasilkan sisa, di mana memberi kesan kepada kesihatan dan alam sekitar. Benih Moringa oleifera (MO) boleh digunakan sebagai bahan ganti semula jadi kepada perapi kimia. Bahan bio-aktif perlu diekstrak daripada benih MO bagi memberi kesan terbaik. Dalam kajian ini, kaedah rawatan menggunakan benih MO adalah dari ekstrak bio-aktif NaCl (1 M) dan ekstrak minyak dari bahan larut hexane, serta serbuk benih tidak dirawat (mentah). Sampel sintetik kotoran mendapan disediakan dengan menggunakan ampaian kaolin (5% w/v). Bentuk kogulan yang paling efektif didapati berdasarkan nilai halaju malar (Vs) dan indeks ketumpatan kotoran mendapan (SVI). Keputusan menunjukkan ekstrak NaCl memberi keputusan terbaik pada halaju malar 0.41 cm/min dan bacaan pada SVI 63.39 ml/g. Nilai SVI lebih besar daripada 150 ml/g menunjukkan kualiti kadaran malar kurang baik berbanding 100 ml/g kajian kawalan semasa kotoran mendapan. Bentuk kogulan yang paling efektif telah dioptimumkan pada tiga keadaan proses: dos benih MO, halaju campuran dan tempoh campuran. Eksperimen dibentuk menggunakan 2 Level Factorial-Design daripada perisian Design-Expert. Keadaan optimum proses adalah pada 3246 mg/l dos benih, 102 rpm halaju campuran, dan tempoh campuran selama 29 min. Benih MO boleh di kategori sebagai kogulan semula jadi dan boleh digunakan sebagai perapi utama bagi kotoran mendapan.


Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.


2020 ◽  
Vol 17 (6) ◽  
pp. 523-539
Author(s):  
Jalpa Patel ◽  
Dhaval Mori

Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.


2020 ◽  
Vol 16 (1) ◽  
pp. 43-60 ◽  
Author(s):  
Priyanka Kriplani ◽  
Kumar Guarve ◽  
Uttam Singh Baghel

Background: Osteoarthritis (OA) ranks fifth among all forms of disability affecting 10% of the world population. Current treatments available are associated with multiple side effects and do not slow down the progression of the disease. Moreover, no such effective treatment is available to date in various systems of medicine to treat osteoarthritis. Curcumin and Arnica have shown evident clinical advances in the treatment of osteoarthritis. Objective: The aim of the present study was to design, optimize and characterize novel herbal transdermal patches of curcumin and Arnica montana using factorial design. Methods: A multiple factorial design was employed to investigate the effect of hydroxypropyl methyl cellulose, ethyl cellulose and jojoba oil on elongation and drug release. Transdermal patches were evaluated by FTIR, DSC, FESEM, ex vivo drug permeation, anti osteoarthritic activity and analgesic activity. Results: Independent variables exhibited a significant effect on the physicochemical properties of the prepared formulations. The higher values of drug release and elongation were observed with the higher concentration of hydroxypropyl methylcellulose and jojoba oil. Anti osteoarthritic activity was assessed by complete Freund's adjuvant arthritis model; using rats and analgesic activity by Eddy's hot plate method, using mice. Combination patch exhibited good anti osteoarthritic and analgesic activity as compare to individual drug patches. Conclusion: The design results revealed that the combination patch exhibited good physicochemical, anti osteoarthritic and analgesic activity for the treatment of osteoarthritis in animals. More plants and their combinations should be explored to get reliable, safe and effective formulations that can compete with synthetic drugs.


2020 ◽  
Vol 10 (3) ◽  
pp. 306-315
Author(s):  
Rupa Mazumder ◽  
Swarnali Das Paul

Background: Atenolol is a commonly used antihypertensive drug of class III BCS category. It suffers from the problem of poor intestinal absorption or permeability thus low bioavailability. The objective of the present study was to enhance the permeability of atenolol by using a suitable technique, which is economical and devoid of using any organic solvent. Methods: The nanocrystal technology by high-pressure homogenization was chosen for this purpose, which is a less expensive and simple method. In this technique, no organic solvent was used. The study was further aimed to characterize prepared nanocrystals in the solid state by Fourier Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD) patterns, particle size, zeta potential, %yield and drug permeation study through isolated goat’s intestine. An in-vivo study was carried out to determine the pharmacokinetic property in comparison to pure drug powder using rats as experimental animals. The formulation design was optimized by a 3(2) factorial design. In these designs, two factors namely surfactant amount (X1) and speed of homogenizer (X2) were evaluated on three dependent variables namely particle size (y1), zeta potential (y2) and production yield (y3). Results: PXRD study indicated the presence of high crystal content in the prepared formulation. These nanocrystal formulations were found with a narrow size range from 125 nm to 652 nm and positive zeta potential of 16-18 mV. Optimized formulations showed almost 90% production yield. Permeability study revealed 90.88% drug release for optimized formulation in comparison to the pure drug (31.22%). The FTIR study also exposed that there was no disturbance in the principal peaks of the pure drug atenolol. This confirmed the integrity of the pure drug and its compatibility with the excipients used. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the pure drug. The higher values of the determination coefficient (R2) of all three parameters indicated the goodness of fit of the 3(2) factorial model. The factorial analysis also revealed that speed of homogenizer had a bigger effect on particle size (-0.2812), zeta potential (-0.0004) and production yield (0.0192) whereas amount of surfactant had a lesser effect on production yield (-370.4401), zeta potential (-43.3651) as well as particle size (-6169.2601). Conclusion: It is concluded that the selected method of nanocrystal formation and its further optimization by factorial design was effective to increase the solubility, as well as permeability of atenolol. Further, the systematic approach of factorial design provides rational evaluation and prediction of nanocrystals formulation on the selected limited number of smart experimentation.


Author(s):  
R. SANTOSH KUMAR ◽  
ANNU KUMARI ◽  
B. KUSUMA LATHA ◽  
PRUDHVI RAJ

Objective: The aim of the current research is optimization, preparation and evaluation of starch tartrate (novel super disintegrant) and preparation of fast dissolving oral films of cetirizine dihydrochloride by employing starch tartrate. Methods: To check the drug excipient compatibility studies of the selected drug (Cetrizine dihydrochloride) and the prepared excipient i. e starch tartrate, different studies like FTIR (Fourier-transform infrared spectroscopy), DSC (Differential scanning calorimetry) and thin-layer chromatography (TLC) were carried out to find out whether there is any interaction between cetirizine dihydrochloride and starch tartrate. The solvent casting method was used for the preparation of fast dissolving films. The prepared films were then evaluated for thickness, folding endurance, content uniformity, tensile strength, percent elongation, in vitro disintegration time and in-vitro dissolution studies. Response surface plots and contour plots were also plotted to know the individual and combined effect of starch tartrate (A), croscarmellose sodium (B) and crospovidone (C) on disintegration time and drug dissolution efficiency in 10 min (dependent variables). Results: Films of all the formulations are of good quality, smooth and elegant by appearance. Drug content (100±5%), thickness (0.059 mm to 0.061 mm), the weight of films varies from 51.33 to 58.06 mg, folding endurance (52 to 67 times), tensile strength (10.25 to 12.08 N/mm2). Fast dissolving films were found to disintegrate between 34 to 69 sec. Percent dissolved in 5 min were found to be more in F1 formulation which confirms that starch tartrate was effective at 1%. Conclusion: From the research conducted, it was proved that starch tartrate can be used in the formulation of fast dissolving films of cetirizine dihydrochloride. The disintegration time of the films was increased with increase in concentration of super disintegrant.


2013 ◽  
Vol 8 (3) ◽  
pp. 155892501300800 ◽  
Author(s):  
Mitra Karimian ◽  
Hossein Hasani ◽  
Saeed Ajeli

This research investigates the effect of fiber, yarn and fabric variables on the bagging behavior of single jersey weft knitted fabrics interpreted in terms of bagging fatigue percentage. In order to estimate the optimum process conditions and to examine the individual effects of each controllable factor on a particular response, Taguchi's experimental design was used. The controllable factors considered in this research are blending ratio, yarn twist and count, fabric structure and fabric density. The findings show that fabric structure has the largest effect on the fabric bagging. Factor yarn twist is second and is followed by fabric density, blend ratio and yarn count. The optimum conditions to achieve the least bagging fatigue ratio were determined.


2011 ◽  
Vol 331 ◽  
pp. 261-264 ◽  
Author(s):  
Qi Ming Zhao ◽  
Shan Yan Zhang

The auxiliary devices of ultrasonic treatment was designed and manufactured. The cotton fabric was desized using 2000L desizing enzyme with the conventional enzyme desizing process and ultrasonic enzyme desizing process respectively. Through the orthogonal experiment, the optimum process conditions of conventional enzyme desizing process and ultrasonic enzyme desizing process were determined. For the conventional enzyme desizing process, the optimized desizing conditions of cotton fabrics were: desizing enzyme dosage was 1.5g/l, temperature was 80°C, PH value was 6, and time was 60mins. The optimum process conditions of ultrasonic enzyme desizing process were: desizing enzyme dosage was 1.5g/l, temperature was 50°C, PH value was 6 and time was 45minutes. The research result indicates that, under the same desizing condition, ultrasonication can improve the desizing percentage and whiteness of cotton fabric, but the fabric strength loss increases slightly. And for the same required desizing percentage, the ultrasonic enzyme desizing process saved time and reduced the temperature of experiments compared with traditional enzyme desizing process


1982 ◽  
Vol 51 (1) ◽  
pp. 19-26 ◽  
Author(s):  
E. M. Jastrebske

Undergraduate men who held neutral positions on a variety of issues were exposed to peer-group opinions whose semantic wording was varied to present either a positive or negative context. Two replications of the procedure using statements of different contents were conducted (each sample n = 40); a 2 × 2 factorial design was used for both replications where the independent variables were direction of semantic wording (positive or negative) and direction of influence from peer ratings (for agreement or disagreement). Support was found for an interaction of the two independent variables wherein conformity increased as a function of congruity between direction of peer opinions and semantic context of stimulus-wording.


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