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.

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.

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.

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.

scholarly journals Development of a BCS Class II Drug Microemulsion for Oral Delivery: Design, Optimization, and Evaluation

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Marwa Tlijani ◽  
Mohamed Ali Lassoued ◽  
Badr Bahloul ◽  
Souad Sfar
Keyword(s):  
Droplet Size ◽  
Oral Delivery ◽  
Classical Method ◽  
Ex Vivo ◽  
Physical Stability ◽  
Class Ii ◽  
Bcs Class Ii ◽  
Everted Gut Sac ◽  
Hydrophilic Lipophilic Balance ◽  
New Perspective

Our work is aimed at exploring the composition and the properties of microemulsion (ME), as a drug delivery system, to enhance the permeability across the gastrointestinal (GI) barrier of fenofibrate, a BCS class II drug. It is a prodrug that is converted rapidly after oral administration into a major active metabolite which is the fenofibric acid. It undergoes a nearly complete presystemic metabolism. Its main drawback is the low bioavailability of the metabolite. A quick selection of excipients was made based on the capacity of solubilization and the value of hydrophilic-lipophilic balance. The classical method of ME development was coupled with the factorial design in order to minimize the droplet size using a low concentration of surfactant. The optimized ME showed a droplet size of 48.5 nm and physical stability. The passive permeability evaluated using Sartorius was 1.6 times higher than that of the free drug. The ex vivo technique, performed using the everted gut sac model, showed a 2.5-fold higher permeability. This suggests that the carrier-mediated uptake/efflux may present the dominant transport mechanism of fenofibrate. The use of the excipients that inhibit GI P-glycoprotein may be a new perspective. Thus, this paper shows that the composition and the characteristics of ME may be explored to increase the permeability of fenofibrate across the GI membrane.

scholarly journals Engineering cocrystals of Paliperidone with enhanced solubility and dissolution characteristics

2021 ◽  
Vol 71 (5) ◽  
pp. 393-409
Author(s):  
Earle Radha-Rani ◽  
Gadela Venkata-Radha
Keyword(s):  
Benzoic Acid ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
X Ray Diffraction ◽  
X Ray ◽  
Water Soluble Drug ◽  
Novel Approach ◽  
Enhanced Solubility ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

In the present study, co-crystals (CCs) of Paliperidone (PPD) with coformers like benzoic acid (BA) and P-amino benzoic acid (PABA) were synthesized and characterized to improve the physicochemical properties and dissolution rate. CCs were prepared by the solvent evaporation (SE) technique and were compared with the products formed by neat grinding (NG) and liquid assisted grinding (LAG) in their enhancement of solubility. The formation of CCs was confirmed by the IR spectroscopy, powder X-ray diffraction and thermal analysis methods. The saturation solubility studies indicate that the aqueous solubility of PPD-BA and PPD-PABA CCs was significantly improved to 1.343±0.162mg/ml and 1.964±0.452mg/ml, respectively, in comparison with the PPD solubility of 0.473mg/ml. This increase in solubility is 2.83-and 3.09-fold, respectively. PPD exhibited a poor dissolution of 37.8% in 60min, while the dissolution of the CCs improved tremendously to 96.07% and 89.65% in 60min. CCs of PPD with BA and PABA present a novel approach to overcome the solubility challenges of poorly water-soluble drug PPD.

scholarly journals Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 548 ◽  
Author(s):  
Serena Bertoni ◽  
Beatrice Albertini ◽  
Nadia Passerini
Keyword(s):  
Solid State ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Class Ii ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Crystalline Solid ◽  
Dissolution Behavior ◽  
Bcs Class Ii

Delivery of poorly water soluble active pharmaceutical ingredients (APIs) by semi-crystalline solid dispersions prepared by spray congealing in form of microparticles (MPs) is an emerging method to increase their oral bioavailability. In this study, solid dispersions based on hydrophilic Gelucires® (Gelucire® 50/13 and Gelucire® 48/16 in different ratio) of three BCS class II model compounds (carbamazepine, CBZ, tolbutamide, TBM, and cinnarizine, CIN) having different physicochemical properties (logP, pKa, Tm) were produced by spray congealing process. The obtained MPs were investigated in terms of morphology, particles size, drug content, solid state properties, drug-carrier interactions, solubility, and dissolution performances. The solid-state characterization showed that the properties of the incorporated drug had a profound influence on the structure of the obtained solid dispersion: CBZ recrystallized in a different polymorphic form, TBM crystallinity was significantly reduced as a result of specific interactions with the carrier, while smaller crystals were observed in case of CIN. The in vitro tests suggested that the drug solubility was mainly influenced by carrier composition, while the drug dissolution behavior was affected by the API solid state in the MPs after the spray congealing process. Among the tested APIs, TBM-Gelucire dispersions showed the highest enhancement in drug dissolution as a result of the reduced drug crystallinity.

scholarly journals Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 407
Author(s):  
Sooho Yeo ◽  
Jieun An ◽  
Changhee Park ◽  
Dohyun Kim ◽  
Jaehwi Lee
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
Promising Alternative ◽  
Dispersion System ◽  
Enhanced Solubility ◽  
Water Soluble Drugs

This study aimed to improve the solubility and dissolution of aprepitant, a drug with poor aqueous solubility, using a phosphatidylcholine (PC)-based solid dispersion system. When fabricating the PC-based solid dispersion, we employed mesoporous microparticles, as an adsorbent, and disintegrants to improve the sticky nature of PC and dissolution of aprepitant, respectively. The solid dispersions were prepared by a solvent evaporation technique and characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, and X-ray powder diffraction. The FTIR results showed that aprepitant interacted with the PC carrier by both hydrogen bonds and van der Waals forces that can also be observed in the interaction between aprepitant and polymer carriers. The solid dispersions fabricated with only PC were not sufficient to convert the crystallinity of aprepitant to an amorphous state, whereas the formulations that included adsorbent and disintegrant successfully changed that of aprepitant to an amorphous state. Both the solubility and dissolution of aprepitant were considerably enhanced in the PC-based solid dispersions containing adsorbent and disintegrant compared with those of pure aprepitant and polymer-based solid dispersions. Therefore, these results suggest that our PC-based solid dispersion system is a promising alternative to conventional formulations for poorly water-soluble drugs, such as aprepitant.

scholarly journals Improved Dissolution of Albendazole from High Drug Loaded Ternary Solid Dispersion: Formulation and Characterization

2021 ◽  
Vol 20 (2) ◽  
pp. 149-158
Author(s):  
Shimul Halder ◽  
MAK Azad ◽  
Hrishik Iqbal ◽  
Madhabi Lata Shuma ◽  
Eva Rahman Kabir
Keyword(s):  
Solid Dispersion ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Drug Carriers ◽  
Physicochemical Characteristics ◽  
Water Soluble ◽  
Dissolution Behavior ◽  
Scanning Calorimetry ◽  
High Drug ◽  
Enhanced Solubility

Bioavailability of a poorly water-soluble drug, e.g., widely used anthelmintic drug Albendazole (ABZ), is very low and thus, to obtain an optimized therapeutic efficacy, the aqueous solubility of such drugs needs to be enhanced. The objective of this study was to develop an effective high drug-loaded solid dispersion (SD) of ABZ with two biocompatible drug carriers, namely Soluplus® and Ludiflash® to improve its physicochemical characteristics. Equilibrium solubility study was performed to choose the optimum polymer ratio among the formulations and it showed up to 50-fold enhanced solubility compared to crystalline ABZ in water. X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) studies of SD-ABZ showed reduced crystallinity of ABZ in the SD. The polymeric carriers, notably Soluplus®, are thought to play a key role in the reduction of crystallinity and molecular polydispersity of ABZ. The dissolution studies in water showed improved dissolution of SD-ABZ compared to crystalline ABZ, with a quick onset of drug release followed by gradual dissolution. However, due to high drug-loading and retention of crystalline ABZ in the sample, the dissolution behavior was not as expected, and may require further studies to optimize the SD-ABZ formulation. Dhaka Univ. J. Pharm. Sci. 20(2): 149-158, 2021 (December)

scholarly journals PREPARATION, CHARACTERIZATION AND DISSOLUTION STUDY OF SPRAY DRIED SOLID DISPERSIONS OF SIMVASTATIN WITH PVP K25 AND AEROSIL 200

2021 ◽  
Vol 10 (6) ◽  
pp. 3806-3812
Author(s):  
Pritam Singh
Keyword(s):  
Drug Release ◽  
Spray Drying ◽  
Solid Dispersions ◽  
Aqueous Solubility ◽  
Class Ii ◽  
Drying Method ◽  
Bcs Class Ii ◽  
Enhanced Dissolution ◽  
Amorphous Nature ◽  
Characterization Studies

BCS class II is well-known for the drugs, having poor aqueous solubility and high permeability. Simvastatin is also categorized as BCS class II, suffering from poor aqueous solubility, affecting its bioavailability. In an attempt to resolve this problem, solid dispersions of simvastatin were prepared by spray-drying method. Solid dispersions of simvastatin with PVP K25 and aerosol in ratio (1:1:1 to 1:5:1) and without aerosil 200 (1:1 to 1:5) were prepared by spray drying method. The dissolution test showed the enhancement of dissolution as compared to the pure drug and nearly equal to marketed formulation “SIMVOTIN 20mg” in both types of formulation, but formulations with aerosil 200 showed faster drug release as compared to the simple formulations without aerosil. The formulation containing the 1:3:1 (simvastatin: PVP K25: Aerosil 200) showed the faster drug release as compared to other formulation that do not contain the Aerosil 200. Other characterization studies were also performed such as FTIR, differential scanning colorimetry and powdered X-ray crystallographic studies. These studies showed the increased amorphous nature of the drug in the formulation, which explain the enhanced dissolution rate of the drug for these formulations.

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.

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