scholarly journals Enhancing the Oral Bioavailability of Candesartan Cilexetil Loaded Nanostructured Lipid Carriers: In Vitro Characterization and Absorption in Rats after Oral Administration

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1047
Author(s):  
Walid Anwar ◽  
Hamdy Dawaba ◽  
Mohsen Afouna ◽  
Ahmed Samy ◽  
Mohammed Rashed ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Candesartan Cilexetil ◽  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Nanostructured Lipid Carriers ◽  
Water Soluble ◽  
Nanostructured Lipid Carrier ◽  
In Vitro Characterization ◽  
Water Soluble Drugs

Candesartan Cilexetil (CC) is a prodrug widely used in the treatment of hypertension and heart failure, but it has some limitations, such as very poor aqueous solubility, high affinity to P-glycoprotein efflux mechanism, and hepatic first-pass metabolism. Therefore, it has very low oral bioavailability. In this study, glyceryl monostearate (GMS) and Capryol™ 90 were selected as solid and liquid lipids, respectively, to develop CC-NLC (nanostructured lipid carrier). CC was successfully encapsulated into NLP (CC-NLC) to enhance its oral bioavailability. CC-NLC was formulated using a hot homogenization-ultrasonication technique, and the physicochemical properties were characterized. The developed CC-NLC formulation was showed in nanometric size (121.6 ± 6.2 nm) with high encapsulation efficiency (96.23 ± 3.14%). Furthermore, it appeared almost spherical in morphology under a transmission electron microscope. The surgical experiment of the designed CC-NLC for absorption from the gastrointestinal tract revealed that CC-NLC absorption in the stomach was only 15.26% of that in the intestine. Otherwise, cellular uptake study exhibit that CC-NLCs should be internalized through the enterocytes after that transported through the systemic circulation. The pharmacokinetic results indicated that the oral bioavailability of CC was remarkably improved above 2-fold after encapsulation into nanostructured lipid carriers. These results ensured that nanostructured lipid carriers have a highly beneficial effect on improving the oral bioavailability of poorly water-soluble drugs, such as CC.

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 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.

The effect of nanonization on poorly water soluble glibenclamide using a liquid anti-solvent precipitation technique: aqueous solubility, in vitro and in vivo study

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81728-81738 ◽  
Author(s):  
Rohan D. Deshpande ◽  
Gowda D. V. ◽  
Naga Sravan Kumar Varma Vegesna ◽  
Rudra Vaghela ◽  
Kulkarni P. K.
Keyword(s):  
Process Parameters ◽  
Oral Bioavailability ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
In Vivo Study ◽  
Precipitation Technique ◽  
Poorly Water Soluble

In the present study, efforts were made to optimize the process parameters of LAS technique for developing GLB NPs, in order to enhance the aqueous solubility as well as oral bioavailability.

Solubility Enhancement Techniques for Poorly Water-Soluble Drugs

2017 ◽  
Vol 10 (3) ◽  
pp. 3701-3708
Author(s):  
Amol S Deshmukh ◽  
Kundan J Tiwari ◽  
Vijay R Mahajan
Keyword(s):  
Plasma Concentrations ◽  
Aqueous Solubility ◽  
Systemic Circulation ◽  
Water Soluble ◽  
Formulation Development ◽  
Poorly Water Soluble Drugs ◽  
Poor Solubility ◽  
New Chemical Entities ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

Solubility is the phenomenon of dissolution of solid in liquid phase to give a homogenous system. Solubility is one of the important parameter to achieve desired concentration of drug in systemic circulation for optimum pharmacological response. Poorly water-soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Poor aqueous solubility is a major problem encountered with formulation development of new chemical entities. There are over 40% of new chemical entities that exhibit poor solubility and low bioavailability. As per BCS classification system, these drugs comes under BCS class II that show poor solubility and high permeability. The bioavailability of these drugs can be dramatically improved by increasing the solubility of these drugs. This review article highlights a number of techniques for enhanc

scholarly journals DEVELOPMENT AND IN VITRO EVALUATION OF SOLID DISPERSIONS OF CANDESARTAN CILEXETIL

2019 ◽  
pp. 233-241
Author(s):  
Bhikshapathi D.v.r.n.
Keyword(s):  
Candesartan Cilexetil ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Solvent Evaporation ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Optimized Design ◽  
Water Soluble Drugs ◽  
Effective Group

Objective The main objective of the present study is systematic development of solid dispersions of Candesartan cilexetil by solvent evaporation method to enhance the solubility and bioavailability. Methods In the present study, eighteen formulations of solid dispersions were prepared with 1:1 and 1:3 ratios of drug: carrier and with and without surfactant. There was significant improvement in the rate of drug release from all 20 solid dispersions and the formulation (SD16) comprising Candesartan: containing Soluplus (1:3 ratio of drug:  Soluplus with 2% SLS as surfactant) by solvent evaporation process. Results Final optimized design SD16 contained maximum drug content of 99.08%. In in vitro dissolution studies it shows greater dissolution rate i.e. 99.7±4.2% associated through additional designs and pure drug. The drug was compatible with all the excipients as per FTIR (Fourier transform infrared spectroscopy). From powder X-ray diffraction (p-XRD) and by (SEM) studies it was evident that crystalline form of Candesartan has been converted into amorphous form within solid dispersion design.  Conclusion From these studies we can accomplish solid dispersions are one of the greatest favorable formulation for Candesartan cilexetil for enhancing the solubility and bioavailability of poorly water soluble drugs in the effective group of hypertension and other cardiac problems.

Optimization of Nanostructured Lipid Carriers of Fenofibrate Using a Box-Behnken Design for Oral Bioavailability Enhancement

2021 ◽  
Vol 18 ◽  
Author(s):  
Huijuan Wang ◽  
Wei Hong ◽  
Xiangyu Li ◽  
Qian Jin ◽  
Weifeng Yea ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Nanostructured Lipid Carrier ◽  
Bioavailability Enhancement ◽  
Box Behnken Design ◽  
Predicted Values

Background: Fenofibrate (FNB) is a commonly used hypolipidemic agent. However, the oral bioavailability of FNB is limited by slow dissolution due to its low solubility. Thus, investigations on novel FNB formulations are necessary for their use. Objective: To enhance the oral bioavailability of FNB using optimized Nanostructured Lipid Carrier (NLC) formulations. Methods: Hot homogenization followed by ultrasonication was used to prepare FNB-NLCs. These formulations were optimized using a Box-Behnken design, where the amount of FNB (X1), a ratio of solid lipid/liquid lipid (X2), and the percentage of emulsifier (X3), were set as independent variables, while the particle size (Y1), and Entrapment Efficiency (EE%) (Y2), were used as dependent factors. An in vitro dissolution test was then performed using a paddle method, while an in vivo pharmacokinetic study of FNB-NLC formulation was performed in rats. Results: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. Results: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. Conclusion: A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.

scholarly journals Solid-State Lipid - Based Lipid Drug Delivery System

2021 ◽  
Vol 001 (01) ◽  
Author(s):  
Mamta Nasit ◽  
Meshva Patel ◽  
Ajay Solanki ◽  
Jayendrakumar Patel
Keyword(s):  
Drug Delivery ◽  
Solid State ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Bioavailability ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Different Types ◽  
Water Soluble Drugs ◽  
Lipid Excipients

In recent time, about 70% of new molecules discovered or under discovery are lipophilic in nature with low aqueous solubility which makes a great challenge for formulation scientists to making these molecules to be have a sufficient aqueous solubility and oral bioavailability. Lipid-based drug delivery system (LBDDS- wide ranging designation for formulations containing a dissolved or suspended drug in lipid excipients) is one of the appropriate approach which gained significant popularity due to their ability to deliver poorly water-soluble drugs with improved solubility and oral bioavailability. Conventional LBDDS, including lipid emulsions, suspensions etc. suffer from various drawbacks limiting their widespread commercialization and use. Therefore, solid-state LBDDS fabricated from conventional LBDDS using different types of solid carriers via various solidification methods eliminated some of the various limitations of conventional LBDDS with great stability. The present review provide overview on the various types of solid state lipid based drug delivery systems, different types of solid carriers use in formulation of solid state lipid based drug delivery system, various solidification techniques for conversion of liquid lipid system to solid dosage form, advantages and some practical limitations of lipid based drug delivery system.

scholarly journals Self-nanoemulsifying System Optimization for Higher Terconazole Solubilization and Non-Irritant Ocular Administration

2020 ◽  
Vol 10 (3) ◽  
pp. 389-398 ◽  
Author(s):  
Carol Yousry ◽  
Pakinam Mohsen Zikry ◽  
Emad Basalious Basalious ◽  
Omaima Naem El-Gazayerly
Keyword(s):  
Chorioallantoic Membrane ◽  
Aqueous Solubility ◽  
System Optimization ◽  
Water Soluble ◽  
Eye Drops ◽  
Therapeutic Uses ◽  
Globule Size ◽  
Hen’S Egg ◽  
Water Soluble Drugs

Purpose: Eye drops’ formulations of poorly water-soluble drugs, offer the advantage of crossing the lipophilic cornea, but their limited aqueous solubility may lead to low ocular bioavailability limiting their therapeutic uses. Terconazole (TZ) is an antifungal drug with low aqueous solubility, restricting its application in ocular fungal infection. Thus, the aim of the work in this study is to enhance TZ solubilization, permitting better ocular permeation and higher bioavailability. To achieve this goal, different self-nanoemulsifying systems (SNESs) were prepared using different oils, surfactants and co-surfactants. Methods: Ternary phase diagrams were constructed to identify self nano-emulsification regions for each oil system examined; either Labrafil® M2125CS or Capryol™ 90. TZ saturated solubility in the different formulated systems were measured and systems showing highest potential for TZ solubilization were selected. The optimized systems were chosen based on their globule size, polydispersity index, self-emulsification characteristics. Finally, TZ release as well as the irritation effect via Hen’s Egg test-chorioallantoic membrane (HET-CAM test) of the optimized system was observed in vitro. Results: The optimized system was formulated using 20% w/w Labrafil® M2125 CS, 50% w/w Tween® 80 and 30% w/w Transcutol® HP. Oil globules showed size range of 15.13 nm and self-emulsification time of 12.80 seconds. The system released 100% of the drug within half an hour compared to 2 hours in case of TZ-suspension. Finally, HET-CAM test showed non-irritating response and normal vascularization of the chorioallantoic membrane. Conclusion: The formulated SNES could be a promising approach to enhance ocular efficacy of TZ.

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