scholarly journals Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

2021 ◽  
Vol 14 (12) ◽  
pp. 1255
Author(s):  
Ju-Hyun Lee ◽  
Chulhun Park ◽  
Kwon-Yeon Weon ◽  
Chin-Yang Kang ◽  
Beom-Jin Lee ◽  
...  
Keyword(s):  
Drug Release ◽  
Amorphous State ◽  
Water Soluble ◽  
Pharmacokinetic Data ◽  
In Vivo Test ◽  
Water Soluble Drug ◽  
Absorption Area ◽  
Poorly Water Soluble

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

AMORPHOUS SOLID DISPERSIONS OF PIOGLITAZONE HYDROCHLORIDE USING CREMOPHOR RH 40 AND POLOXAMER 188: IN VITRO AND IN VIVO EVALUATION

INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (01) ◽  
pp. 45-55
Author(s):  
R. P Swain ◽  
B. B Subudhi ◽  
Keyword(s):  
Solid Dispersions ◽  
Amorphous State ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
In Vivo Evaluation ◽  
In Vivo Test ◽  
Water Soluble Drug

The study was aimed to improve dissolution and bioavailability of developed stable amorphous solid dispersions (SDs) of pioglitazone hydrochloride (PGH), a poorly water soluble drug. TGA showed compatibility with the polymers. The significant change in melting pattern of the PGH observed in the DSC thermograms supported by XRD patterns and SEM indicated change from crystalline to amorphous state. Prevention of recrystallization during storage suggested stability of formulation. Cremophor RH 40 based SD (solvent method) remarkably increased the dissolution within 15 min and was supported by dissolution parameters (Q15, IDR, RDR, % DE, f1, f2). In vivo test showed significantly (p < 0.05) higher AUC0-t and Cmax, which were about 4.46 and 4.84 times that of pure drug, respectively. Cremophor RH 40 was found to be a suitable carrier for SM for preparation of SDs of PH as evident from increased dissolution and bioavailability.

In Vitro-In Vivo Correlation for Solid Dispersion of a Poorly Water-Soluble Drug Efonidipine Hydrochloride

2020 ◽  
Vol 21 (5) ◽  
Author(s):  
Xu Cheng ◽  
Jianlong Gao ◽  
Jiaqi Li ◽  
Gang Cheng ◽  
Meijuan Zou ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Water Soluble ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

scholarly journals COMPARISON AND CHARACTERIZATION OF INCLUSION COMPLEXES AND SOLID DISPERSIONS IN ENHANCEMENT OF DISSOLUTION RATE OF POORLY WATER SOLUBLE DRUG

2018 ◽  
Vol 10 (5) ◽  
pp. 173
Author(s):  
Radha Rani Earle ◽  
Rambabu Jammu ◽  
Lakshmi Usha ◽  
Ratna Kanth Lingam
Keyword(s):  
Drug Release ◽  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Peg 6000 ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Objective: The purpose of the present study was to enhance solubility and dissolution characteristics of indomethacin by preparing inclusion complexes with hydroxypropyl β-cyclodextrin (HP β-CD) and solid dispersions with PEG 6000 to enhance its in vitro drug release and to further formulate it as a tabletMethods: Solid dispersions (SDs) and inclusion complexes (ICs) of Indomethacin with PEG 6000 and HP β-CD respectively were prepared to enhance the dissolution rate of this poorly water-soluble drug belonging to BCS class II. A comparison was made between two systems: solid dispersions with PEG 6000 obtained using melting and solvent evaporation technique, inclusion complexes with HP β-CD prepared by kneading technique. SDs were prepared in 1:1, 1:2, 1:3 and ICs in 1:0.25, 1:0.5, 1:1 w/w ratios of drug: polymer. Both the systems were characterized by FTIR, SEM, DSC, X-RD.Results: The dissolution of indomethacin increased with the increase in the concentration of the polymers. F4 and F9 formulations showed complete drug release in less than 30 min. Dissolution studies indicated that cyclodextrin complexes showed a better enhancement of dissolution rate when compared to solid dispersions. CDs were found to be more effective than PEGs at lower concentrations. These formulations were further compressed as tablets.Conclusion: The FTIR and DSC studies showed that no interactions existed between the drug and the polymer.

scholarly journals Electrospinning Preparation of Timosaponin B-II-Loaded PLLA Nanofibers and Their Antitumor Recurrence Activities In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Zhonghua Huo ◽  
Yan Qiu ◽  
Zhuling Chu ◽  
Peng Yin ◽  
Wenquan Lu ◽  
...  
Keyword(s):  
Drug Carrier ◽  
Amorphous State ◽  
Water Soluble ◽  
Sustained Delivery ◽  
Water Soluble Drug ◽  
Release Studies ◽  
Long Time ◽  
Model Drug

Poly(L-lactic)-acid (PLLA) as a drug carrier and a water-soluble drug timosaponin B-II (TB-II) as a model drug were selected to prepare drug-loaded nanofibers by electrospinning. The average diameters of pure PLLA nanofibers and TB-II-loaded nanofibers were 212.5 ± 68.5, 219.7 ± 57.8, 232.8 ± 66.9, and 232.9 ± 97.7 nm, respectively. DSC and XRD results demonstrated that TB-II was well incorporated into the nanofibers in an amorphous state. FI-TR spectroscopy indicated that TB-II had good compatibility with PLLA. In vitro release studies showed that TB-II was rapidly released from the nanofibers within 6 h, followed by a gradual release for long time. In vivo biosafety test revealed no noticeable toxicity of these TB-II nanofibers. The TB-II released from the nanofibers had obvious inhibition effect against human hepatocellular carcinoma SMMC 7721 cells both in vivo and in vitro. It was confirmed that the TB-II-loaded nanofibers were a sustained delivery system which could effectively inhibit the tumor growth and recurrence after surgery.

NANO-SIZED SOLID DISPERSION OF A POORLY WATER-SOLUBLE DRUG

2012 ◽  
pp. 31-35
Author(s):  
Truong Dinh Thao Tran ◽  
Ha Lien Phuong Tran ◽  
Nghia Khanh Tran ◽  
Van Toi Vo
Keyword(s):  
Drug Release ◽  
Droplet Size ◽  
Solid Dispersion ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
Particle Size Reduction ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

Purposes: Aims of this study are dissolution enhancement of a poorly water-soluble drug by nano-sized solid dispersion and investigation of machenism of drug release from the solid dispersion. A drug for osteoporosis treatment was used as the model drug in the study. Methods: melting method was used to prepare the solid dispersion. Drug dissolution rate was investigated at pH 1.2 and pH 6.8. Drug crystallinity was studied using differential scanning calorimetric and powder X-ray diffraction. In addition, droplet size and contact angle of drug were determined to elucidate mechanism of drug release. Results: Drug dissolution from the solid dispersion was significantly increased at pH 1.2 and pH 6.8 as compared to pure drug. Drug crystallinity was changed to partially amorphous. Also dissolution enhancement of drug was due to the improved wettability. The droplet size of drug was in the scale of nano-size when solid dispersion was dispersed in dissolution media. Conclusions: nano-sized solid dispersion in this research was a successful preparation to enhance bioavailability of a poorly water-soluble drug by mechanisms of crystal changes, particle size reduction and increase of wet property.

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