Development and characterization of ternary system for solubility enhancement of a second-generation COX-II inhibitor

2016 ◽  
Vol 5 (12) ◽  
pp. 5163
Author(s):  
Santosh Girani* ◽  
Shidallingapa Zalki ◽  
Mahantesh Kavatekar ◽  
Ajay Shahapur ◽  
Vitthal K. Vijapure
Keyword(s):  
Ternary Systems ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Complexing Agents ◽  
High Permeability ◽  
Bcs Class Ii ◽  
Enhanced Solubility

Etoricoxib is a highly selective COX-II inhibitor, used to treat pains of different etiologies. Etoricoxib has low aqueous solubility (201g/ml) and high permeability and therefore classified as BCS class II drug. By formulating these drugs with cyclodextrins as inclusion complexes have shown to increase the bioavailability. Cyclodextrins when used as complexing agents, enhance the solubility of poor water soluble lipophilic drugs. The objective of the present work is to formulate Etoricoxibcyclodextrin complexes by using ternary systems as Citric acid, Tartaric acid and PVP K-30 in order to enhance solubility and evaluate the enhanced solubility by in-vitro dissolution.

scholarly journals Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Shivarani Eesam ◽  
Jaswanth S. Bhandaru ◽  
Chandana Naliganti ◽  
Ravi Kumar Bobbala ◽  
Raghuram Rao Akkinepally
Keyword(s):  
Aqueous Solubility ◽  
Sem Analysis ◽  
Water Soluble ◽  
High Permeability ◽  
Poorly Water Soluble Drugs ◽  
Drug Discovery And Development ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Dissolution In Vitro

Abstract Background Increasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals. Results The formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days). Conclusion It may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

scholarly journals ENHANCEMENT OF SOLUBILITY AND BIOAVAILABILITY OF BCS CLASS-II AMBRISENTAN: IN VITRO, IN VIVO AND EX VIVO ANALYSIS

2022 ◽  
pp. 67-74
Author(s):  
RAHUL RADKE ◽  
NEETESH K. JAIN
Keyword(s):  
Solid Dispersion ◽  
Ex Vivo ◽  
Class Ii ◽  
Water Soluble ◽  
Pure Form ◽  
In Vitro Dissolution ◽  
Drug Solubility ◽  
Bcs Class Ii

Objective: The aim of this investigation was to enhance the solubility and bioavailability of the BCS class II poorly water-soluble drug ambrisentan by solid dispersion (SD) techniques using Gelucire 50/13 as a hydrophilic carrier. Methods: Solid dispersion of ambrisentan was prepared by kneading method using different dug: carrier ratios. Prepared SD was characterized for solubility, drug content, percentage yield, in vitro dissolution, ex vivo permeation and bioavailability. Solid-state characterization was performed by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Results: All the SDs formulations showed increase in drug solubility and dissolution when compared with its pure form. Aqueous solubility of the drug was found to be increased 8.23 fold in SD. DSC study showed that endothermic peak of the drug was disappeared in spectra of SD, confirming its amorphous conversion, XRD study revealed the reduction to almost absence of specific high-intensity peaks of drug which confirmed the reduction of crysatallinity of ambrisentan in SD. SEM of optimized SD formulation demonstrates the complete encapsulation and solubilization drug. In vitro dissolution study showed that optimized SD formulation (ASD4) gives the faster drug release of 101.5% in 60 min, as compare to its pure form and other SD formulations. Conclusion: Solid dispersion ASD4 prepared with 1:4 drug to carrier ratio showed the highest drug solubility and in vitro dissolution. The ex vivo and in vivo studies performed on optimized formulation ASD4 showed enhancement in drug permeability and bioavailability in Gelucire 50/13 based SD formulation.

scholarly journals Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

2021 ◽  
Vol 11 (2) ◽  
pp. 23-30
Author(s):  
Anil Kumar ◽  
Umesh K. Jain ◽  
Ajay Patel
Keyword(s):  
Drug Release ◽  
Stearic Acid ◽  
Aqueous Solubility ◽  
Class Ii ◽  
Water Soluble ◽  
Fibric Acid Derivative ◽  
Formulation Development ◽  
Bcs Class Ii ◽  
Paraffin Oil

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs. Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

scholarly journals In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility

2021 ◽  
Vol 14 (11) ◽  
pp. 1089
Author(s):  
Hakan Nazlı ◽  
Burcu Mesut ◽  
Yıldız Özsoy
Keyword(s):  
Drug Delivery ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Ternary Phase Diagrams ◽  
Enhanced Solubility ◽  
Porous Carriers ◽  
Drug Precipitation ◽  
Precipitation Inhibitors ◽  
Preformulation Studies

Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.

Design, Optimization and Evaluation of Repaglinide Self-Nanoemulsifying Drug Delivery for Enhanced Solubility

2017 ◽  
Vol 10 (6) ◽  
pp. 3920-3928
Author(s):  
Mahalaxmi K ◽  
Sailu Ch
Keyword(s):  
Drug Delivery ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Antidiabetic Drug ◽  
Water Soluble Drug ◽  
Enhanced Solubility ◽  
Poorly Water Soluble ◽  
Capmul Mcm ◽  
Poorly Water Soluble Drug

The aim of study was to develop self-nanoemulsifying systems of poorly water-soluble drug repaglinide, which is an antidiabetic drug in the class of medications known as meglitinides. Solubility of repaglinide in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). Surfactants and oil was selected based on solubility studies were further screened for their efficiency in formulation. Acrysol K 150, Kolliphor EL and Capmul MCM were selected as oil, surfactant and co-surfactant respectively. Formulation F8 was found to be optimized formulation on the basis of in vitro dissolution studies, particle size and zeta potential. The optimized formulation was then subjected to stability studies and was found to be stable after 6 months. Thus, SNEDDS were found to be influential in improving the release performance of repaglinide, indicating their potential to improve the solubility and oral bioavailability of repaglinide.  

scholarly journals FORMULATION AND EVALUATION OF SOLID SELF-EMULSIFYING DRUG DELIVERY SYSTEM OF GLICLAZIDE

2016 ◽  
Vol 8 (11) ◽  
pp. 144
Author(s):  
Suwarna R. Deshmukh ◽  
Suparna S. Bakhle ◽  
Kanchan P. Upadhye ◽  
Gouri R. Dixit
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Delivery ◽  
Tween 80 ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Water Soluble Drug

Objective: Gliclazide (GCZ) is a widely prescribed anti-diabetic drug belongs to class IΙ under BCS and exhibit low and variable oral bioavailability due to its poor aqueous solubility. The present investigations highlight the development of solid self-emulsifying drug delivery system (solid-SEDDS) for improved oral delivery of the poorly water-soluble drug, GCZ.Methods: Various oils, surfactant and co-surfactant, were screened for their emulsification ability. Ternary phase diagrams were plotted to identify the zone of micro-emulsification. Liquid SEDDS of the drug were formulated using lemon oil as the oil phase, tween 80, as the surfactant, and labrasol, as the co-surfactant. The optimized liquid SEDDS was transformed into free-flowing powder using florite R as the adsorbent. Results: Self-emulsifying powder retained the self-emulsifying property of the liquid SEDDS. The morphology of solid-SEDDS from scanning electron microscopy studies demonstrated the presence of spherical, granular particles indicating good flowing ability. X-ray powder diffraction studies confirmed solubilization of the drug in the lipid excipients and/or transformation of a crystalline form of the drug to amorphous form. In vitro dissolution studies revealed enhanced release of the drug from solid-SEDDS as compared to plain drug and marketed formulation.Conclusion: Thus it can be concluded that solid-SEDDS, amenable for the development of solid dosage form, can be successfully developed using florite R with the potential of enhancing the solubility, dissolution rate, and bioavailability of the drug.

scholarly journals Effect of inclusion of citric acid and Lutrol® F-68 on ziprasidone and β-cyclodextrin complexation: Characterization, solubility and dissolution studies

2020 ◽  
Vol 11 (4) ◽  
pp. 280-284
Author(s):  
Vaishali Yogesh Londhe ◽  
Sreevidya Ramesh Krishnan
Keyword(s):  
Citric Acid ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vitro Dissolution ◽  
Scanning Calorimetry ◽  
Solubility Study ◽  
Dissolution Studies ◽  
Enhanced Solubility ◽  
Ft Ir

Ziprasidone (ZPR) is an antipsychotic agent having less solubility. It is used for the treatment of schizophrenia. Complexation of hydrophobic drugs with cyclodextrins leads to enhanced solubility and dissolution. In this study, inclusion complexes were prepared by different methods, using ZPR, β-cyclodextrin (β-CD), and different auxiliary agents like hydrophilic polymer and hydroxy acid (1:1:0.5) to improve the aqueous solubility. The characterization of the ternary complexes was carried out using solubility study, Differential scanning calorimetry (DSC), Powder X-ray diffraction (PXRD), Fourier transformation infrared spectroscopy (FT-IR) and in vitro dissolution studies. DSC, XRD, and FT-IR studies showed interaction in drug, cyclodextrin, and auxiliary agents which are confirmed by enhancement of solubility and dissolution. Spray-dried dispersion showed less crystallinity and higher solubility as compared to the kneading method for both citric acid and Lutrol® F-68. Thus, the investigation concludes that the presence of the auxiliary agent has a synergistic action on complexation with cyclodextrin, which helps to modify the physicochemical properties of the drug.

NATEGLINIDE SILICA LIPIDHYBRID PARTICLES FOR IMPROVED SOLUBILITY

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (06) ◽  
pp. 73-78
Author(s):  
Shradha Tiwari ◽  
Shailesh Wadher ◽  
Surendra Gattani
Keyword(s):  
Oral Delivery ◽  
Porous Silica ◽  
Aqueous Solubility ◽  
Class Ii ◽  
Water Soluble ◽  
Bcs Class Ii ◽  
Enhanced Solubility ◽  
Ft Ir ◽  
Tablet Dosage ◽  
Highly Porous

Porous silica-based drug delivery systems have shown substantial potential for improving the oral delivery of poorly water-soluble drugs.The major problem with nateglinide, a BCS Class II drug, is pHdependent solubility, limited aqueous solubility, poor dissolution and variable bioavailability. The aim of the present investigation was to develop a lipid-based solid formulation of nateglinide, as a strategy to improve both the solubility and the dissolution rate of the drug in a tablet dosage form. The silica lipid hybrid (SlH) particles were formulated using Miglyol812 and Acrysol el 135 as liquid lipid vehicles as well aslabrasol and Transcutol HP as surfactants.Nateglinide was dissolved in different lipids and later adsorbed on highly porous silica Sylloid PF244 to obtain free-flowing powders. The prepared nateglinide SlH was characterized by FT-IR, DSC, and XRD.Nateglinide SlH was evaluated for solubility and dissolution. SlH of NTG prepared with Miglyol 812 and Transcutol HP enhanced solubility of NTG 57.21 fold. From the study, it may be concluded that the oral solid lipid-based formulation, SlH has an improved potential for enhancing solubility and dissolution of BCS class II drugs like nateglinide.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Sign in / Sign up

Export Citation Format

Share Document