scholarly journals Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Padmanabha Rao Amarachinta ◽  
Garima Sharma ◽  
Noufel Samed ◽  
Ananda Kumar Chettupalli ◽  
Madhusudhan Alle ◽  
...  
Keyword(s):  
Drug Release ◽  
Central Composite Design ◽  
Transdermal Delivery ◽  
Therapeutic Potential ◽  
Entrapment Efficiency ◽  
Gradual Reduction ◽  
Transdermal Delivery System ◽  
Hypertensive Drug ◽  
Central Composite

Abstract Background Carvedilol, the anti-hypertensive drug, has poor bioavailability when administered orally. Ethosomes-mediated transdermal delivery is considered a potential route of administration to increase the bioavailability of carvedilol. The central composite design could be used as a tool to optimize ethosomal formulation. Thus, this study aims to optimize carvedilol-loaded ethosomes using central composite design, followed by incorporation of synthesized ethosomes into hydrogels for transdermal delivery of carvedilol. Results The optimized carvedilol-loaded ethosomes were spherical in shape. The optimized ethosomes had mean particle size of 130 ± 1.72 nm, entrapment efficiency of 99.12 ± 2.96%, cumulative drug release of 97.89 ± 3.7%, zeta potential of − 31 ± 1.8 mV, and polydispersity index of 0.230 ± 0.03. The in-vitro drug release showed sustained release of carvedilol from ethosomes and ethosomal hydrogel. Compared to free carvedilol-loaded hydrogel, the ethosomal gel showed increased penetration of carvedilol through the skin. Moreover, ethosomal hydrogels showed a gradual reduction in blood pressure for 24 h in rats. Conclusions Taken together, central composite design can be used for successful optimization of carvedilol-loaded ethosomes formulation, which can serve as the promising transdermal delivery system for carvedilol. Moreover the carvedilol-loaded ethosomal gel can extend the anti-hypertensive effect of carvedilol for a longer time, as compared to free carvedilol, suggesting its therapeutic potential in future clinics.

scholarly journals Enhancement and Extended Release of the Anti-hypertensive Drug Carvedilol using Optimized Ethosomal Gel via Transdermal Route

2020 ◽  
Author(s):  
Padmanabha Rao Amarachinta ◽  
Noufel Samed ◽  
Ananda Kumar Ch. ◽  
Madhusudhan Alle ◽  
Jin-Chul Kim
Keyword(s):  
Drug Release ◽  
Transdermal Delivery ◽  
Physical Appearance ◽  
Entrapment Efficiency ◽  
Hepatic Metabolism ◽  
In Vitro Drug Release ◽  
Rapid Action ◽  
Alternative Drug ◽  
Hypertensive Drug

Abstract BackgroundCarvedilol, a popular anti-hypertensive drug, when orally administered has very poor bioavailability on the account of undergoing hepatic metabolism and therefore it becomes primal to explore an alternative drug delivery route for carvedilol. For a drug to be delivered by undergoing the least number of stages of metabolism and achieve high target specificity, transdermal delivery is the most preferred route. Hence, a study was conducted to test the potential of ethosomes as a candidate for transdermal delivery of carvedilol. A statistical study by using Central Composite Design (CCD) was also conducted for optimizing the quantity of the primary constituents present in the ethosomes. The optimized ethosomal formulation was then incorporated into a hydrogel to prepare the ethosomal gel.ResultsThe optimized formulated ethosomal suspension and the ethosomal gel were undergone physicochemical, compatibility and in-vitro drug release studies along with characterization studies. The incorporation of the ethosomes into the hydrogel proved to be effective for skin application thereby ensuring better transdermal delivery. The optimized ethosomal gel has showed credible physical appearance, spreadability, viscosity and in-vitro drug release. The pharmacodynamic studies conducted on Wister rats revealed that the anti-hypertensive action was gradual and sustained lasting up to a period of 24 hours. The stability studies conducted also showed that prepared formulations maintained its consistency within the range for the measured parameters of physical appearance, rheological properties and entrapment efficiency for a period of 3 months.Conclusions The incorporation of the drug loaded into hydrogel and its effect on regulating systolic blood pressure in a sustained way lasting 24 hours proved to be better than the present available marketed formulation which has a rapid action with the anti-hypertensive effect lasting only for 10 hours. The chosen route for delivering the drug transdermally hence proved to be effective with better enhancement and permeation capability and shows the high potential of ethosomes to be considered for novel delivery of other anti-hypertensive drugs.

Development of Sertaconazole Nitrate Loaded Nanostructured Lipid Carriers Gel Using Central Composite Design: In-vitro and Ex-vivo Evaluation

2020 ◽  
Vol 10 ◽  
Author(s):  
Moreshwar Patil ◽  
Pallavi Bhagade ◽  
Meghana Amale ◽  
Sandeep Sonawane ◽  
Sanjay Kshirsagar
Keyword(s):  
Drug Release ◽  
Central Composite Design ◽  
Total Lipid ◽  
High Speed ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Nanostructured Lipid Carriers ◽  
Topical Formulation ◽  
Central Composite

Aim: The aim of this study was to develop effective topical antifungal formulation containing sertaconazole nitrate. Background: Sertaconazole nitrate, topical antifungal was incorporated in solid-liquid lipid nanostructures and gelled further for topical application. Objective: The objective of this investigation was to develop a topical formulation containing sertaconazole nitrate which was incorporated in the solid state of matrix to prolong the release in deep skin infection and hence reduce the application frequency. Methods: The nanostructured lipid carriers of sertaconazole nitrate were developed by high speed homogenization followed by ultrasonication using Estosoft-GTS® (glyceryl tristearate) as a solid lipid, oleic acid as liquid lipid and Tween 80 as an emulsifier. Central composite design was used to optimize total lipid concentration and fraction of liquid lipid in the total lipid and its effect on entrapment efficiency and drug release was determined. Results: The carrier particles had an average size of 366.3 nm; entrapment efficiency in between 50.66% to 87.36%; cumulative drug release up to 92.90% and zeta potential of 7.43 mV. Characterization by FTIR indicated no negative interaction between drug and excipients, XRD showed disappearance of crystalline peaks of the encapsulated drug while DSC revealed complete solubilization of the drug. About 99.6% of drug was estimated by HPLC method. The drug release from gel and cream was 25.04% and 72.97% respectively. The lipid and gel excipients did not interfere with antifungal activity of the drug. Conclusion: The developed nanocarriers loaded gel were stable. It prolonged the drug release (for 24 hours) than marketed cream. It could be a promising concept for topical delivery of antifungal and anti-inflammatory materials.

Formulation and evaluation of Cassia tora phytosomal gel using central composite design.

2021 ◽  
Vol 14 ◽  
Author(s):  
Leander Corrie ◽  
Raghunandan Gundaram ◽  
Latha Kukatil
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
Therapeutic Activity ◽  
In Vitro Drug Release ◽  
Cassia Tora ◽  
Dependent Variables ◽  
Antifungal Effects ◽  
Two Parameters ◽  
Central Composite

Background:: Cassia tora has been classified as an antifungal agent, but no optimized formulation for improved drug penetration has been developed. Objective:: The present work aimed to formulate Cassia tora extract (CTE) phytosomal gel that could be used for its antifungal effects and improved therapeutic activity. Materials and Methods: The CTE phytosomes were formulated by varying the concentration of lecithin (0.15-0.25% w/v) and speed of rotation (100-160 rpm). A 22 factorial design was applied by taking the above two parameters as independent variables and vesicular size and entrapment efficiency as dependent variables. The phytosomes were also evaluated for polydispersity index, zeta potential and in vitro drug release. The optimized phytosomes of CTE were further developed into a gel, the optimized gel was also evaluated and stability studies were conducted. Results and Discussion: The optimized CTE phytosome showed a vesicular size of ~ 124 nm and entrapment efficiency of 95%. The CTE phytosomes showed a drug release of 58.79% in 24 hours following Higuchi's order of release. The CTE phytosomes were formulated into a gel by using 1% Carbopol 934 and were evaluated for pH, viscosity and homogeneity. The formulated gel showed better penetration than conventional gel and stability changes indicated no major changes to the CTE phytosomal gel. Conclusion: The optimized gel had better penetration and drug release than the conventional gel. Its therapeutic activity, therefore can be estimated to be enhanced.

scholarly journals ATENOLOL MICROPARTICLES BY TWO-FACTOR TWO-LEVEL CENTRAL COMPOSITE DESIGN

2020 ◽  
pp. 192-201
Author(s):  
ARTI SHARMA ◽  
SUNIL K BATRA
Keyword(s):  
Drug Release ◽  
Central Composite Design ◽  
Release Kinetics ◽  
Liquid Paraffin ◽  
Entrapment Efficiency ◽  
Solvent Evaporation ◽  
Size Analysis ◽  
Release Kinetic ◽  
New Delhi ◽  
Central Composite

Objective: The objective of this research was to formulation, optimization, and evaluation of gastric-mucoadhesive microparticles which contains selective β1 receptor antagonist atenolol. Methods: The following chemicals were used, atenolol (Gangwal Chemicals Pvt. Ltd., Mumbai), ethyl cellulose (EC) (Loba Chemie Pvt. Ltd., Mumbai), Carbopol 940 (Loba Chemie Pvt. Ltd., Mumbai), liquid paraffin (Arora Pharmaceuticals Pvt. Ltd., New Delhi), and Span 80 (Central Drug House (P) Ltd., New Delhi). Microparticles were prepared by the emulsification solvent evaporation technique using polymers of Carbomer 934p (CP) and EC. Disc formulations were prepared by direct compression technique from microparticles. Microparticles of combined polymers were designed according to 22 factorial central composite design (CCD), taking EC concentration and surfactant concentration as the independent variables. A total of 13 batches were prepared. The dependent variables were percentage of % drug released and % entrapment efficiency. Results and Discussion: All evaluation tests were done for the prepared 13 formulations, such as percentage entrapment efficiency, percentage drug release, swelling index, percentage yield, and particle size analysis. The entrapment efficiency of optimized formulation was found to be 72.02%. The entrapment efficiency increases with increase in EC concentration and stirring speed. Optimized formulation was further subjected to study of drug release kinetics based on the R2 value; it was observed that Korsmeyer Peppas release kinetic model was found to be best suited for formulation of atenolol with EC: carbopol 934 by solvent evaporation method. Conclusion: The optimized formulation of microparticles containing atenolol was found to be homogeneous, good appearance and had well flow properties and better release kinetics.

FORMULATION AND EVALUATION OF MICROSPHERES FOR NASAL DELIVERY OF ANTI-HYPERTENSIVE DRUG

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (10) ◽  
pp. 21-26
Author(s):  
S. S Shelake ◽  
◽  
R. M Mhetre ◽  
S. V Patil ◽  
S. S Patil ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Nasal Delivery ◽  
In Vivo Studies ◽  
Oral Drug ◽  
Hypertensive Drug

Lisinopril is used in the treatment of hypertension and heart failure in myocardial infarction and also in diabetic nephropathy. It is very poorly absorbed from GIT. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The microspheres prepared by emulsion solvent evaporation method were characterized for encapsulation efficiency, drug loading, particle size, surface morphology, degree of swelling, ex vivo mucoadhesion, drug release and ex vivo diffusion studies. Entrapment efficiency of microspheres was in range of 84.95±0.50% to 97.44±0.61% mucoadhesion was 83.76% and 94.41% and drug release up to 40 minutes was 53.66% to 88.32%. In ex vivo studies, the microspheres showed good bioavailability by nasal route compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol-based formulation for the delivery of lisinopril.

scholarly journals Transdermal delivery of solid lipid nanoparticles of ketoprofen for treatment of arthritis

2019 ◽  
Vol 8 (3) ◽  
pp. 627-636
Keyword(s):  
Drug Release ◽  
Transdermal Delivery ◽  
Solid Lipid Nanoparticles ◽  
Entrapment Efficiency ◽  
Controlled Drug Release ◽  
Lipid Nanoparticles ◽  
In Vitro Drug Release ◽  
Solid Lipid ◽  
Anti Inflammatory

Ketoprofen (KP) is a 2-(3-benzolphenyl) propionic acid with anti-inflammatory, analgesic and antipyretic properties. It belongs to BCS Class II drug. It also has a short half-life of 120 minutes. Drugs acidic nature causes gastric irritation which is a major limitation. The present work aims to develop and evaluate solid lipid nanoparticles (SLN) to provide transdermal drug delivery. SLN loaded gel will enhance the solubility of Ketoprofen thereby increasing bioavailability giving controlled drug release. Solid lipid nanoparticles were prepared by solvent injection followed by probe sonication method. Cetyl palmitate was used as lipid and Tween80 as a surfactant. Batches were prepared by varying the concentration of the lipid phase and the surfactant phase. The solid lipid nanoparticles were evaluated for particle size analysis, drug entrapment efficiency, zeta potential and in vitro drug release study. Differential scanning calorimetry (DSC) and Powder X-ray diffraction (PXRD) study were done to study crystallinity behavior.SLN was studied for its anti-inflammatory activity. F4 batch of SLN was incorporated into gel and evaluated for drug content, pH, viscosity, in-vitro diffusion and ex-vivo diffusion study. SLN were successfully prepared. Among the batches F1-F9, F4 batch was selected based upon the size, entrapment efficiency, stability and drug release. The resultant solid lipid nanoparticles showed entrapment efficiency of 78.24%. The solubility was improved by 50 fold. The particle size was 250 nm, PDI was 0.398 and zeta potential -21.98mV. In-vitro drug release of gel from F4 SLN batch showed controlled drug release in 8 hours. Transdermal delivery of SLN retaining its anti-inflammatory activity was successfully developed.

scholarly journals CENTRAL COMPOSITE DESIGN FOR FORMULATION AND OPTIMIZATION OF LONG-ACTING INJECTABLE (LAI) MICROSPHERES OF PALIPERIDONE PALMITATE

2021 ◽  
pp. 87-98
Author(s):  
SANDIP MALI ◽  
NISHANT OZA
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Central Composite Design ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Paliperidone Palmitate ◽  
Burst Release ◽  
Mean Particle Size ◽  
Long Acting ◽  
Central Composite

Objective: The aim of the present study was to optimize long-acting injectable (LAI) microspheres of Paliperidone palmitate (PP) for treatment of schizophrenia using face-centered central composite design (FC-CCD). Methods: In this study, poly lactic-co-glycolic acid (PLGA) based LAI microspheres of paliperidone palmitate (PP) were formulated by using FC-CCD. LAI microspheres were developed by using oil in water (O/W) emulsion solvent evaporation technique. On the basis of preliminary trials, FC-CCD was employed to check effect of independent variables such as drug polymer ratio (X1), homogenization speed (X2) and rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4), and drug release on day 60 (Y5) were considered as dependent variables and statistically evaluation performed by using design expert 12 software. Morphology of prepared microspheres was studied by using the scanning electron microscopy (SEM) technique, while particle size was analyzed by laser diffraction technique. In vitro drug release studies were performed using a controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study were performed to analyze any changes in crystal behavior or to detect any chemical bonding between ingredients. 13C NMR and 1H NMR techniques were used to analyze end-capping and monomer ratio in developed microspheres. Results: The factorial batches mean particle size was found to be 38 µm to 104 µm and drug loading were found between 27.2 % to 47.2%. Mathematical modelling of drug release kinetics revealed that near zero-order drug release of checkpoint formulations. Endcap analysis and molar ratio of formulated microspheres were found to be ester end cap and ~75:25, respectively. Morphologically all the prepared samples were found to be spherical in shape and smooth surface. FTIR data showed no significant interactions occurred between drug and excipients. The actual responses of checkpoint formulations were observed within 5% variation of predicted values. Conclusion: The prepared microspheres showed promising results of morphology, particle size, drug loading, entrapment efficiency, burst release and drug release on day 60. The successful predictive designs models were achieved from employed FC-CCD.

Central composite design for development and evaluation of floating-mucoadhesive tablets of Gliclazide

2020 ◽  
Vol 15 ◽  
Author(s):  
Manoj Bansal ◽  
Ravinder Verma ◽  
Vineet Mittal ◽  
Deepak Kaushik
Keyword(s):  
Drug Release ◽  
Sodium Bicarbonate ◽  
Central Composite Design ◽  
Lag Time ◽  
Compression Technique ◽  
Gastric Residence Time ◽  
Mucoadhesive Tablets ◽  
High Level ◽  
Central Composite

Background: Gliclazide assimilation rate from the gastrointestinal (GI) tract is slow and inconstant which may be either due to poor dissolution or poor permeability of the drug across the GI membrane. Objective: The present investigation deals with the formulation of floating-mucoadhesive tablets of gliclazide for oral administration using central composite design by direct compression technique using HPMC K4M and Carbopol 934 as release controlling polymers and sodium bicarbonate as effervescent agent. Methods: Central composite design was employed to quantify the effect of three factors-concentration of HPMC K4M (X1), concentration of Carbopol 934 (X2) and concentration of sodium bicarbonate (X3) on floating lag time, drug release and mucoadhesive time of the formulation. Results: The results revealed that floating lag time decreases with rise in concentration of sodium bicarbonate, drug release was highest at low levels of HPMC and Carbopol and mucoadhesive time was highest at high level of Carbopol. Conclusion: The optimized batch (F-7) shows mucoadhesive time of 23 minutes 27 seconds, floating lag time of 22 seconds and in vitro cumulative percentage of drug release 86.73 % in 10h. From the investigation, it can be summarized that the gastro-retentive drug delivery can be utilized to enhance bioavailability and gastric residence time of drugs.

Design and Optimization of Itraconazole Loaded SLN for Intranasal Administration Using Central Composite Design

2020 ◽  
Vol 10 (6) ◽  
pp. 884-891
Author(s):  
Sarvjeet S. Rana ◽  
Shailendra Bhatt ◽  
Manish Kumar ◽  
Anuj Malik ◽  
Jai B. Sharma ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Intranasal Administration ◽  
Ex Vivo ◽  
Entrapment Efficiency ◽  
Scanning Calorimetry ◽  
Solid Lipid ◽  
Ex Vivo Study ◽  
Central Composite

Introduction: Solid Lipid nanoparticles (SLN) are comprising of a solid lipid core with a mean diameter between 50 and 1000 nm. SLN is an advanced carrier system to traditional colloidal carriers such as emulsion, liposomes, and polymeric microparticles. Objective: The objective of this study was to formulate SLN of Itraconazole (ITZ) for intranasal administration. Methods: ITZ-loaded SLN were prepared by high pressure homogenization technique using the Central Composite Design (CCD). The concentration of surfactant (X1) and drug to lipid ratio (X2) was considered as independent variables, whereas particle size (Y1) and percentage entrapment efficiency (Y2) were considered as a response. The compatibility of ingredients with the drug was tested using differential scanning calorimetry. SLN were characterized for their particle size, entrapment efficiency, transmission electron microscopy, in vitro drug release, and ex vivo study. Results: The solid lipid nanoparticles were successfully prepared using high pressure homogenization technique and glyceryl monostearate was used as solid lipid. The lipid ratio significantly increases the particle size as well as entrapment efficiency. The particle size and (%) entrapment efficiency of optimized formulation were found to be 29 nm and 78.9%, respectively. The differential scanning calorimetry confirmed that the drug existed in amorphous form. Nasal histopathology study on sheep mucosa revealed that the developed SLN was non-toxic and safe to use for intranasal administration. The results of ex vivo study showed that the Higuchi pattern of drug release was followed. The in vitro release studies showed the significant difference in drug release from ITZ-loaded SLN compared to plain ITZ-solution. Conclusion: ITZ-loaded SLN were successfully prepared and validated. The best batch was selected based on the desired particle size, and EE which is an important characteristic for SLN formulations. The developed formulations were nontoxic as determined by histo-pathological studies.

Formulation and In Vivo Evaluation of Mucoadhesive Micro-spheres of Rebamipide, a Mucoprotective Drug for GIT Disorders

2018 ◽  
Vol 11 (3) ◽  
pp. 4089-4097
Author(s):  
Bhikshapathi D. V. R. N. ◽  
Kanteepan P
Keyword(s):  
Drug Release ◽  
Entrapment Efficiency ◽  
In Vivo Studies ◽  
Amino Acid Derivative ◽  
Release Mechanism ◽  
In Vivo Evaluation ◽  
In Vitro Drug Release ◽  
Percentage Yield

Rebamipide, an amino acid derivative of 2-(1H)-quinolinone, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. The current research study aimed to develop novel gastro-retentive mucoadhesive microspheres of rebamipide using ionotropic gelation technique. Studies of micromeritic properties confirmed that microspheres were free flowing with good packability. The in vitro drug release showed the sustained release of rebamipide up to 99.23 ± 0.13% within 12 h whereas marketed product displayed the drug release of 95.15 ± 0.23% within 1 h. The release mechanism from microspheres followed the zero-order and Korsmeyer-Peppas (R2 = 0.915, 0.969), respectively. The optimized M12 formulation displayed optimum features, such as entrapment efficiency 97%, particle size 61.94 ± 0.11 µm, percentage yield 98%, swelling index 95% and mucoadhesiveness was 97%. FTIR studies revealed no major incompatibility between drug and excipients. SEM confirmed the particles were of spherical in shape. Optimized formulation (M12) were stable at 40°C ± 2°C/75% RH ± 5% RH for 6 months. In vivo studies were performed and kinetic parameters like Cmax, Tmax, AUC0-t, AUC0-∞, t1/2, and Kel  were calculated. The marketed product Cmax (3.15 ± 0.05 ng/mL) was higher than optimized formulation (2.58 ± 0.03 ng/mL). The optimized formulation AUC0-t (15.25 ± 1.14 ng.hr/mL), AUC0-∞ (19.42 ± 1.24 ng.hr/mL) was significantly higher than that of marketed product AUC0-t (10.21 ± 1.26 ng.hr/mL) and AUC0-∞ (13.15 ± 0.05 ng.hr/mL). These results indicate an optimized formulation bioavailability of 2.5-fold greater than marketed product.  

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