Enhancing the aqueous solubility and dissolution of olanzapine using freeze-drying

The aim of the present study was to develop an olanzapine freeze-dried tablet (FDT). The solubility and dissolution rate of poorly water-soluble olanzapine was improved by preparing a freeze-dried tablet of olanzapine using the freeze-drying technique . The FDT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was poured in to the pockets of blister packs and then was subjected to freezing and lyophilisation. The FDT was characterised by DSC, XRD and SEM and was evaluated for saturation solubility and dissolution. The samples were stored in a stability chamber to investigate their physical stability. Results obtained by DSC and X-ray were analysed and showed the crystalline state of olanzapine in FDT transformation to the amorphous state during the formation of FDT. Scanning electron microscope (SEM) results suggest reduction in olanzapine particle size. The solubility of olanzapine from the FDT was observed to be nearly four and a half times greater than the pure drug. Results obtained from dissolution studies showed that olanzapine FDT significantly improved the dissolution rate of the drug compared with the physical mixture (PM) and the pure drug. More than 90% of olanzapine in FDT dissolved within 5 minutes, compared to only 19.78% of olanzapine pure drug dissolved over the course of 60 minutes. In a stability test, the release profile of the FDT was unchanged, as compared to the freshly prepared FDT after 90 days of storing.

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Enhancement of Solubility and Dissolution Rate of Poorly Water Soluble Drug using Cosolvency and Solid Dispersion Techniques

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2008.1.4.6 ◽

1970 ◽

Vol 1 (4) ◽

pp. 349-356

Author(s):

Meka Lingam ◽

Vobalaboina Venkateswarlu

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Physicochemical Characterization ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

Peg 400 ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

The low aqueous solubility of celecoxib (CB) and thus its low bioavailability is a problem. Thus, it is suggested to improve the solubility using cosolvency and solid dispersions techniques. Pure CB has solubility of 6.26±0.23µg/ml in water but increased solubility of CB was observed with increasing concentration of cosolvents like PEG 400, ethanol and propylene glycol. Highest solubility (791.06±15.57mg/ml) was observed with cosolvency technique containing the mixture of composition 10:80:10%v/v of water: PEG 400: ethanol. SDs with different polymers like PVP, PEG were prepared and subjected to physicochemical characterization using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), solubility and dissolution studies. These studies reveals that CB exists mainly in amorphous form in prepared solid dispersions of PVP, PEG4000 and PEG6000 further it can also be confirmed by solubility and dissolution rate studies. Solid dispersions of PV5 and PV9 have shown highest saturation solubility and dissolution rate

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RESEARCH AND DEVELOPMENT OF DIAZEPAM SOLID DISPERSION POWDER USING NATURAL POLYMERS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.27975 ◽

2018 ◽

Vol 10 (5) ◽

pp. 220

Author(s):

Uditi Handa ◽

Kamal Saroha

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Water Soluble ◽

Natural Polymers ◽

Drug Content ◽

Ftir Studies ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Pure Drug ◽

Poorly Water Soluble Drug

Objective: The objective of this study was to enhance the solubility and dissolution rate of a poorly water-soluble drug by solid dispersion (SD) technique, in order to conduct an investigation of the effect of these natural hydrophilic polymers on release mechanism from SD.Methods: The SD of diazepam (DZM) were prepared by using modified sodium alginate (SA) and modified guar gum (GG) in different drug: polymer ratios (1:1 and 1:2) by using physical mixture method (PM) and fusion method (FM). Further, the formulations were characterized for calibration curve, Fourier transforms infrared spectroscopy (FTIR) studies, % age practical yield, drug content estimation, solubility studies, dissolution studies.Results: The pure drug and SD were characterized by pre and post-formulations studies. The %age practical yield ranged from 92.9±0.25 to 49±0.57%, and the drug content estimation ranged from 99.34±0.40 to 65.25±0.25 %. The FTIR studies shown that the compatibility between pure drug and natural polymers was stable. All the SD showed improved solubility as compared to the pure drug (PD). SD prepared with modified SA (1:2) by PM and FM shown the huge enhancement of solubility and dissolution rate of the DZM. This can be specific to the improvement in wettability and dispersibility, as well as enhances the drug amorphous fraction.Conclusion: On the basis of the research study, the SD technique shows the enhancement in the solubility of poorly water-soluble drug using natural polymers. SD containing natural polymers prepared with PM and FM shown the remarkable improvement in the release outline compared with PD, DZM.

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IMPROVEMENT OF WATER SOLUBILITY AND IN VITRO DISSOLUTION RATE OF DEFLAZACORT BY COMPLEXATION WITH Β-CYCLODEXTRIN THROUGH FREEZE DRYING PROCESS

INDIAN DRUGS ◽

10.53879/id.57.07.12243 ◽

2020 ◽

Vol 57 (07) ◽

pp. 70-73

Author(s):

Nilesh S Kulkarni ◽

Pallavi D Gitte ◽

Manojkumar K Munde ◽

Shashikant N. Dhole

Keyword(s):

Dissolution Rate ◽

Freeze Drying ◽

Water Solubility ◽

Water Soluble ◽

In Vitro Dissolution ◽

Resonance Spectroscopy ◽

Cyclodextrin Complex ◽

Water Soluble Polymer ◽

Freeze Dried

Deflazacort is a poorly water-soluble drug and is practically insoluble in water. The objective of this study was to improve the solubility of deflazacort by using as solubility enhancer β-cyclodextrin and also to study the effect of the water-soluble polymer PEG 4000 on solubility of the deflazacort:β-cyclodextrin binary system. The inclusion complexes of deflazacort with β-cyclodextrin in 1:1 w/w, 1:2 w/w and 1:3 w/w proportions were prepared by kneading, microwave irradiation and freeze-drying techniques. The in vitro dissolution study showed improved dissolution rate for deflazacort for freeze-dried binary deflazacort: β-cyclodextrin 1:2 w/w complex, as compared to ternary deflazacort:β-cyclodextrin: PEG 6000 1:2 w/w complexes, plain deflazacort, physical mixtures and complexes prepared by kneading and microwave technique. This was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction study, scanning electron microscopy and 1 H nuclear magnetic resonance spectroscopy study. Thus, deflazacort:β-cyclodextrin complex with improved solubility was successfully developed using freeze drying technique.

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Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide

Future Journal of Pharmaceutical Sciences ◽

10.1186/s43094-020-00083-5 ◽

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.

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Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502013000300019 ◽

2013 ◽

Vol 49 (3) ◽

pp. 571-578 ◽

Cited By ~ 8

Author(s):

Payal Hasmukhlal Patil ◽

Veena Sailendra Belgamwar ◽

Pratibha Ramratan Patil ◽

Sanjay Javerilal Surana

Keyword(s):

Dissolution Rate ◽

Hydroxypropyl Methylcellulose ◽

Microwave Treatment ◽

Water Soluble ◽

Fusion Method ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Wetting Properties ◽

Poorly Soluble ◽

Poorly Water Soluble

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

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PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i4.24964 ◽

2018 ◽

Vol 11 (4) ◽

pp. 393

Author(s):

Moon Rajkumar ◽

Gattani Surendra

Keyword(s):

Dissolution Rate ◽

Antipsychotic Agent ◽

Aqueous Solubility ◽

In Vivo Study ◽

Scanning Calorimetry ◽

Antisolvent Precipitation ◽

Enhanced Solubility ◽

Pure Drug

Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

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REVIEW ARTICLE: SOLUBILITY ENHANCEMENT BY SOLID DISPERSION

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2017.v9i3.19583 ◽

2017 ◽

Vol 9 (3) ◽

pp. 15

Author(s):

A. N. Patil ◽

D. M. Shinkar ◽

R. B. Saudagar

Keyword(s):

Solid Dispersion ◽

Aqueous Solubility ◽

Water Soluble ◽

Full Potential ◽

Drug Selection ◽

Formulation Development ◽

Poorly Water Soluble Drugs ◽

New Chemical Entities ◽

Water Soluble Drugs ◽

Poorly Water Soluble

Enhancement of solubility, dissolution rate and bioavailability of the drug is a very challenging task in drug development, nearly 40% of the new chemical entities currently being discovered are poorly water soluble drugs. The solubility behaviour of the drugs remains one of the most challenging aspects in formulation development. This results in important products not reaching the market or not achieving their full potential. Solid dispersion is one of the techniques adopted for the formulation of such drugs and various methods are used for the preparation of solid dispersion. Solid dispersion is generally prepared with a drug which is having poor aqueous solubility and hydrophilic carrier. This article review various methods and concept of solid dispersion, criteria for drug selection, advantage and disadvantage, characterization, and application.

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Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants

Journal of Pharmacy and Pharmacology ◽

10.1111/j.2042-7158.1987.tb05117.x ◽

1987 ◽

Vol 39 (10) ◽

pp. 769-773 ◽

Cited By ~ 20

Author(s):

Hirofumi Takeuchi ◽

Tetsurou Handa ◽

YOshiaki Kawashima

Keyword(s):

Dissolution Rate ◽

Spray Drying ◽

Water Soluble ◽

Deposition Method ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

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Engineering cocrystals of Paliperidone with enhanced solubility and dissolution characteristics

Arhiv za farmaciju ◽

10.5937/arhfarm71-32997 ◽

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.

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