LIQUISOLID COMPACTS: AN INNOVATIVE APPROACH FOR DISSOLUTION ENHANCEMENT

The challenge faced by the majority of the pharmaceutical products is the poor solubility of the drug candidates which leads to low bioavailability. Liquisolid compact is one of the emerging techniques that enhances the dissolution of poorly water soluble drugs. Liquisolid system mentions to the formulation made by the transforming the liquid drug, either in the form of suspension or solution in non volatile solvents into a dry, non-sticky, free-flowing and compactable powder mixtures. This is achieved by mixing the suspension or solution of the drug with appropriate carriers and coating agents. The technology has the ability to increase aqueous solubility, rate of dissolution and absorption of poorly soluble drug by keeping it in molecularly dispersed form leading to its improved bioavailability when compared to conventional tablets. Liquisolid technology is the impending approach for enhancing the solubility of poorly water-soluble drug by adopting simple manufacturing process and low production cost.

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Combined Use of Polymers and Porous Materials to Enhance Cinnarizine Dissolution

Pharmaceutical Sciences ◽

10.15171/ps.2019.44 ◽

2019 ◽

Vol 25 (4) ◽

pp. 331-337

Author(s):

Maryam Maghsoodi ◽

Fatemeh Shahi

Keyword(s):

Porous Materials ◽

Dissolution Rate ◽

Water Soluble ◽

Scanning Calorimetry ◽

Water Soluble Drug ◽

Dissolution Behaviour ◽

Water Soluble Drugs ◽

Poorly Soluble ◽

Precipitation Inhibitor ◽

Poorly Water Soluble

Background: Loading of poorly water-soluble drugs on the porous materials has attracted great interest as an effective approach for enhancement of dissolution rate of drugs. The Aerosil (Ae) with porous structure is expected to facilitate the dissolution of drugs which is generally associated with precipitation. Thus, the purpose of this investigation was thus to develop a formulation which combines a precipitation inhibitor and a poorly soluble drug loaded Ae. Methods: A poorly water-soluble drug, Cinnarizine (CNZ) was used as a model, and Eudragit L100 (Eu) was used as a precipitation inhibitor. Formulations were produced by solvent evaporation and characterized by FT-IR and differential scanning calorimetry (DSC). Dissolution experiments were carried out in phosphate buffer (pH 6.8) under non-sink conditions. Results: DSC thermograms revealed that no crystalline structure of CNZ was present in CNZ-loaded Ae formulations and no long-range order was arranged upon loading of CNZ into Ae. In dissolution test, the CNZ-loaded Ae physically blended with Eu achieved a remarkedly higher CNZ concentration over the plain CNZ and over the CNZ-Eu co-loaded Ae. The dissolution rate of CNZ from the CNZ-loaded Ae was enhanced with increasing Ae amount and the dissolution was maximum when the ratio of CNZ: Ae was 1:10 CNZ: Ae. In addition, the precipitation inhibition was increased when the amount of Eu was high. Conclusion: The results of this work revealed that the dissolution behaviour of CNZ-loaded Ae is enhanced by physically blending of Eu as a suitable precipitation inhibitor.

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

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2012.5.4 ◽

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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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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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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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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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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Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

Polymers ◽

10.3390/polym12081679 ◽

2020 ◽

Vol 12 (8) ◽

pp. 1679

Author(s):

Thao T.D. Tran ◽

Phuong H.L. Tran

Keyword(s):

Solid Dispersion ◽

Solid Dispersions ◽

Water Soluble ◽

Dissolution Enhancement ◽

Formulation Development ◽

Poorly Water Soluble Drugs ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Insoluble Polymers

In recent decades, solid dispersions have been demonstrated as an effective approach for improving the bioavailability of poorly water-soluble drugs, as have solid dispersion techniques that include the application of nanotechnology. Many studies have reported on the ability to change drug crystallinity and molecular interactions to enhance the dissolution rate of solid dispersions using hydrophilic carriers. However, numerous studies have indicated that insoluble carriers are also promising excipients in solid dispersions. In this report, an overview of solid dispersion strategies involving insoluble carriers has been provided. In addition to the role of solubility and dissolution enhancement, the perspectives of the use of these polymers in controlled release solid dispersions have been classified and discussed. Moreover, the compatibility between methods and carriers and between drug and carrier is mentioned. In general, this report on solid dispersions using insoluble carriers could provide a specific approach and/or a selection of these polymers for further formulation development and clinical applications.

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Dissolution study of Spironolactone by using solid dispersion technique

Stamford Journal of Pharmaceutical Sciences ◽

10.3329/sjps.v4i2.7776 ◽

2012 ◽

Vol 4 (2) ◽

pp. 42-47

Author(s):

Irwin Dewan ◽

SM Ashraful Islam ◽

Mohammad Shahriar

Keyword(s):

Drug Delivery ◽

Solid Dispersion ◽

Release Rate ◽

Solid Dispersions ◽

Water Soluble ◽

Poloxamer 407 ◽

Water Soluble Drug ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Dispersion Technique

The main objective of the current study was to formulate poorly water soluble drug Spirinolactone by using solid dispersion technique in order to achieve a better dissolution rate which would further help in enhancing oral bioavailability. Solid dispersions were prepared using two methods; solvent method and fusion method. Solid dispersion was prepared by using polymers, such as Hydroxy propylymethyl cellulose (HPMC 6cp), Hydroxy propyl cellulose (HPC), Sodium carboxymethylcellulose (Na-CMC), Povidone K12, Povidone K30, Poloxamer 407. Solid dispersions containing Spironolactone with HPC (96.81%), HPMC 6cp (93.05%), Poloxamer 407 (90.84%) and Na-CMC (89.93%) provided higher release rate than the release rate of solid dispersion containing only Spironolactone (35.27%), and Spironolactone with Povidone K12 (76.17%), Povidone K30 (67.92%). So the present study revealed that the solid dispersion may be an ideal means of drug delivery system for poorly water soluble drugs. Further study in this field was required to establish these drug delivery systems so that in future it can be used effectively in commercial basis.DOI: http://dx.doi.org/10.3329/sjps.v4i2.7776S. J. Pharm. Sci. 4(2) 2011: 42-47

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Application of Hydrotropic Solubilization in Spectrophotometric Estimation of Lornoxicam from Tablets

International Scholarly Research Notices ◽

10.1155/2014/810128 ◽

2014 ◽

Vol 2014 ◽

pp. 1-4 ◽

Cited By ~ 1

Author(s):

Sindhu Abraham ◽

Rajamanickam Deveswaran ◽

Sharon Furtado ◽

Srinivasan Bharath ◽

Varadharajan Madhavan

Keyword(s):

Aqueous Solubility ◽

Cost Effective ◽

Water Soluble ◽

Alkaline Solutions ◽

Primary Dysmenorrhoea ◽

Cyclooxygenase 1 ◽

Water Soluble Drugs ◽

Label Claim ◽

Poorly Water Soluble ◽

Hydrotropic Agent

Lornoxicam is a selective cyclooxygenase-1 and cyclooxygenase-2 inhibitor that exhibits anti-inflammatory, analgesic, and antipyretic activities. It is used in osteoarthritis and rheumatoid arthritis; and in treatment of postoperative pain and primary dysmenorrhoea. Lornoxicam is completely insoluble in water but soluble in alkaline solutions. Hydrotropic solubilization is a technique used to increase the aqueous solubility of poorly water-soluble drugs and the present study was aimed at developing a hydrotropic technique to increase the solubility of lornoxicam, using 2 M sodium benzoate as the hydrotropic agent. Beer’s law was obeyed in the concentration range of 4–24 μg/mL at 381 nm. The solubility of lornoxicam in distilled water considerably increased with the addition of a hydrotropic agent. The analysis of tablets indicated good correlation between the amounts estimated and label claim. The LOD and LOQ of lornoxicam were found to be 0.34 μg/mL and 1.038 μg/mL, respectively, indicating good sensitivity of the proposed method. The percentage recovery was found to be 99.99%–100.21%. Thus the proposed method is new, simple, environmentally friendly, accurate, and cost effective and can be successfully employed in routine analysis of lornoxicam in tablets.

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