SOLUBILITY AND DISSOLUTION ENHANCEMENT OF BCS CLASS II DRUG PIROXICAM BY SOLID DISPERSION

Background: Eplerenone (EPL) is a BCS class II drug, thus, having the poor water solubility. The poor water solubility of this drug leads to the poor dissolution and ultimately shows the poor bioavailability. To overcome this problem, the solid dispersion of EPL was prepared in this study. Methods: This was accomplished by using the solvent melt method as the solid dispersion technique. In this method Pluronic F-68 and F-127 was used as the carrier and different formulations were prepared using the varying in ratio of a drug and carrier (1:1, 1:2, 1:3, 1:4, 1:5). The mixture of drug solution and carrier were prepared at 70oC, using the digital magnetic stirrer. The resultant mixture was dried at 40oC in hot air oven and optimized EPL-solid dispersion was undergone for their characterization using drug content, drug entrapment efficiency (%) and drug loading content (%), Scanning Electron Microscopy (SEM), Infra-Red spectroscopy, Differential Scanning Calorimetery (DSC), stability study and in-vitro dissolution studies. Results: The result indicated that there was no interaction between EPL and Pluronics (Pluronic F-68 & F-127), and optimized formulation (P127-2) of EPL-solid dispersion have encapsulation efficiency > 95%. Experimental work also showed that optimized formulation has 31.7% of drug loading content which was greater than other existing solid dispersion having less than 30% of drug loading content. Out of different batches, the optimized batch exhibits the faster dissolution rate in comparison of other batches. It released the almost total amount of drug (98.96%) in 30 minutes. The stored ESM-solid dispersion also exhibited their remarkable stability and remains in solid state, when it was exposed to 25oC/60% relative humidity and room temperature (38ºC) for two months. Such stability was confirmed by DSC method. The DSC thermogram of optimized formulation exhibited a melting endotherm at onset temperature of 160oC, a peak temperature of 165oC and a heat of fusion of 25.68 J/gm. Simirly, DSC thermogram of physical mixture of bulk EPL/pluronic F-127 also exhibited the onset of temperature at 165oC, and a peak temperature at 171oC. Thus, result indicated that both sample showed the almost similar DSC pattern and no one sample alter their state after the treatment of temperature and humidity used in stability testing. SEM study was also performed in this research and result indicated that the particle size of optimized formulation was varied and having the irregular matrices due to porous nature of the carrier. Conclusion: Based on different findings it can be concluded that solvent melt method could be a potential method for preparing the solid dispersion of EPL like BCS class-II Drugs and will be able to solve the dissolution and solubilization related problem of poorly soluble drugs.

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Formulation and Characterization of Glimepiride Nanoparticles for Dissolution Enhancement

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666190422160115 ◽

2020 ◽

Vol 10 (5) ◽

pp. 649-663

Author(s):

Reena Siwach ◽

Parijat Pandey ◽

Harish Dureja

Keyword(s):

Drug Release ◽

Dissolution Rate ◽

Oral Absorption ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Class Ii ◽

Dissolution Enhancement ◽

In Vitro Drug Release ◽

Bcs Class Ii

Background: The rate-limiting step in the oral absorption of BCS class II drugs is dissolution. Their low solubility is one of the major obstacles in the process of drug development. Dissolution rate can be increased by decreasing the particle size to the nano range, eventually leading to increased bioavailability. Objective: : In the present study, glimepiride loaded nanoparticles were prepared to enhance the dissolution rate. The aim of the work was to examine the effect of polymer-drug ratio, solvent-antisolvent ratio and speed of mixing on in vitro release of glimepiride. Methods: Glimepiride is an antidiabetic drug belonging to the BCS class II drugs. The polymeric nanoparticles were formulated according to Box-Behnken Design (BBD) using nanoprecipitation technique. The prepared nanoparticles were evaluated for in vitro drug release, loading capacity, entrapment efficiency, and percentage yield. Result: It was found that NP-8 has maximum in vitro drug release and was selected as an optimized batch. Analysis of Variance (ANOVA) was applied to the in vitro drug release to study the fitness and significance of the model. The batch NP-8 showed 70.34 ± 1.09% in vitro drug release in 0.1 N methanolic HCl and 92.02 ± 1.87% drug release in phosphate buffer pH 7.8. The release data revealed that the nanoparticles followed zero order kinetics. Conclusion: The study revealed that the incorporation of glimepiride into gelucire 50/13 resulted in enhanced dissolution rate.

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

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2022v14i1.43347 ◽

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.

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IMPROVING SOLUBILITY OF BCS CLASS II DRUGS USING SOLID DISPERSION: A REVIEW

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v4i3.844 ◽

2014 ◽

Vol 4 (3) ◽

Author(s):

Sweta Mehta ◽

Nisha Mary Joseph ◽

Fitsum Feleke ◽

S Palani

Keyword(s):

Solid Dispersion ◽

Class Ii ◽

Bcs Class Ii

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Design of Experiment Approach to Assess The Effect Of Formulation Variables On Extrusion And Spheronization Of Telmisartan And Cilostazol Loaded Pellets And Its Pharmacokinetic Study

Current Drug Therapy ◽

10.2174/1566523221666210301103849 ◽

2021 ◽

Vol 16 ◽

Author(s):

Kalpana Patel ◽

Prutha Godhani ◽

Hemangini Patel ◽

Vaishali Thakkar ◽

Tejal Gandhi ◽

...

Keyword(s):

Inclusion Complex ◽

Solid Dispersion ◽

Pharmacokinetic Study ◽

Class Ii ◽

Phase Solubility ◽

Solubility Study ◽

Drug Content ◽

Bcs Class Ii ◽

Apparent Solubility ◽

Phase Solubility Study

Background: Solubility is an important parameter that affects availability of drug in systemic circulation. Drugs having poor solubility belonging to BCS class II eventually results in lower dissolution and bioavailability. Hence, improvement of solubility is a challenging task. Hence the present work focusses on using solid dispersion and inclusion complex approach for both telmisartan and cilostazol belonging to BCS Class II drugs. Objective: The present study was carried out to improve apparent solubility of telmisartan and cilostazol (BCS-Class II drugs) and optimization as pellets along with its pharmacokinetic study. Methods: Phase solubility study was carried out to screen the excipients such as, PVPK30, PVA, HPMC E5 and β-CD. Solvent evaporation method was adopted to prepare the solid dispersions and inclusion complex of both the drugs. Pellets were optimized by extrusion spheronization method using 32 factorial design and characterized by morphology, drug content, DSC, FTIR, XRD, SEM, in-vitro studies and drug content study Results: Phase solubility study showed improved apparent solubility of telmisartan with HPMC E5 (1:3) by solid dispersion and cilostazol with β-CD (1:3) using inclusion complexation method. Drug characterization did not reveal any incompatibility. Formulation was optimized on the basis of acceptable pellet properties, including acceptable spherical shape and micromeritics properties. The percent friability of all batches was found to be less than 1%. The optimized pellets of both drugs prepared with micro crystalline cellulose provided desirable maximum release with acceptable release profile. Conclusion: The formulated pellets when studied in vivo showed superior pharmacokinetic profile. The drawback associated with apparent solubility and bioavailability of both drugs can thus be alleviated by use of novel pellet formulation.

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Enhancement of Solubility and Dissolution Rate of BCS Class-II Fluvoxamine Tablets using Solvent Evaporation Solid Dispersion Technique

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i31b31689 ◽

2021 ◽

pp. 44-53

Author(s):

Martha Srinivas ◽

Anoop Singh

Keyword(s):

Solid Dispersion ◽

Solid Dispersions ◽

Research Work ◽

Class Ii ◽

Solvent Evaporation ◽

Peg 6000 ◽

Bcs Class Ii ◽

Dispersion Mechanism ◽

Poorly Soluble ◽

Poorly Soluble Drug

Aim: This research work was aimed to formulate Enhancing the solubility of Poorly soluble drug i.e. Fluvoxamine tablets by the solvent evaporation method, Fluvoxamine medicament is a selective serotonin reuptake inhibitor (SSRI) antidepressant agent. Purpose: The BCS class II drug Fluvoxamine consist low aqueous solubility and low oral bioavailability, for this reason to improve the biological performance of Fluvoxamine drug by solid dispersion mechanism. Methodolgy: The drug Fluvoxamine was formulated by using solvent evaporation technique, solid dispersions of Fluvoxamine were prepared with different carriers in different ratios of PEG 6000 & Mannitol (1:1, 1:2 and 1:3). Results: Results of prepared solid dispersions of Fluvoxamine by solid dispersion method Finally by comparing all the formulations, formulation (SF3) containing Fluvoxamine and PEG 6000 (1:3) shows better results. Conclusion: Here we concluded that the poorly soluble drug solubility improving by solvent evaporation solid dispersion mechanism, and also developed six Fluvovamine formulations (FDF1-FDF6) during this FDF4 shows maximum (98.9±0.8%) drug release at the end of time.

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