Formulation, development and evaluation of injectable formulation of Aspirin

The objective of this study was to develop and manufacture a stable parenteral formulation for Aspirin, a non steroidal anti-inflammatory agent. The solubility and stability of the drug was determined. Solubility studies suggested that Aspirin exhibited poor aqueous solubility but showed appreciable solubility in non-aqueous solvents. Based on the preformulation studies, a lyophilized parenteral formulation containing 25 mg/mL of Aspirin was prepared in a solvent system containing of 80% v/v water and 20% v/v polyethylene glycol-400 (PEG-400). Rubber closures, filter membranes, and liquid transfer tubing were selected on the basis of compatibility studies. The formulation was subjected to accelerated stability studies. After reconstitution with sterile water for injection, Aspirin injection was stable for a period of 8 hr at 2°C to 8°C. Accelerated stability studies suggested that the lyophilized product should be kept at controlled room temperature for longterm storage. The proposed non-aqueous solvent concentration used, are known to safe hence, toxicities/safety related issues may not raise. The proposed techniques would be economical, convenient and safe. Thus, the study opens the chances of preparing lyophilized formulation of poorly-water soluble drugs.

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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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Solubility Enhancement Techniques for Poorly Water-Soluble Drugs

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2017.10.3.1 ◽

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

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Engineering Cocrystals of Poorly Water-Soluble Drugs to Enhance Dissolution in Aqueous Medium

Pharmaceutics ◽

10.3390/pharmaceutics10030108 ◽

2018 ◽

Vol 10 (3) ◽

pp. 108 ◽

Cited By ~ 44

Author(s):

Indumathi Sathisaran ◽

Sameer Dalvi

Keyword(s):

Crystal Engineering ◽

Halogen Bonding ◽

Aqueous Solubility ◽

Pharmaceutical Formulation ◽

Water Soluble ◽

Formulation Development ◽

Poorly Water Soluble Drugs ◽

Enhanced Solubility ◽

Water Soluble Drugs ◽

Poorly Water Soluble

Biopharmaceutics Classification System (BCS) Class II and IV drugs suffer from poor aqueous solubility and hence low bioavailability. Most of these drugs are hydrophobic and cannot be developed into a pharmaceutical formulation due to their poor aqueous solubility. One of the ways to enhance the aqueous solubility of poorlywater-soluble drugs is to use the principles of crystal engineering to formulate cocrystals of these molecules with water-soluble molecules (which are generally called coformers). Many researchers have shown that the cocrystals significantly enhance the aqueous solubility of poorly water-soluble drugs. In this review, we present a consolidated account of reports available in the literature related to the cocrystallization of poorly water-soluble drugs. The current practice to formulate new drug cocrystals with enhanced solubility involves a lot of empiricism. Therefore, in this work, attempts have been made to understand a general framework involved in successful (and unsuccessful) cocrystallization events which can yield different solid forms such as cocrystals, cocrystal polymorphs, cocrystal hydrates/solvates, salts, coamorphous solids, eutectics and solid solutions. The rationale behind screening suitable coformers for cocrystallization has been explained based on the rules of five i.e., hydrogen bonding, halogen bonding (and in general non-covalent bonding), length of carbon chain, molecular recognition points and coformer aqueous solubility. Different techniques to screen coformers for effective cocrystallization and methods to synthesize cocrystals have been discussed. Recent advances in technologies for continuous and solvent-free production of cocrystals have also been discussed. Furthermore, mechanisms involved in solubilization of these solid forms and the parameters influencing dissolution and stability of specific solid forms have been discussed. Overall, this review provides a consolidated account of the rationale for design of cocrystals, past efforts, recent developments and future perspectives for cocrystallization research which will be extremely useful for researchers working in pharmaceutical formulation development.

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

Pharmaceutics ◽

10.3390/pharmaceutics12111047 ◽

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics12050407 ◽

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.

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Dendrimers as Pharmaceutical Excipients: Synthesis, Properties, Toxicity and Biomedical Applications

Materials ◽

10.3390/ma13010065 ◽

2019 ◽

Vol 13 (1) ◽

pp. 65 ◽

Cited By ~ 21

Author(s):

Ana Santos ◽

Francisco Veiga ◽

Ana Figueiras

Keyword(s):

Drug Efficacy ◽

Aqueous Solubility ◽

Pharmaceutical Formulations ◽

The United States ◽

Water Soluble ◽

European Medicines Agency ◽

Uniform Size ◽

Pharmaceutical Excipients ◽

Synthesis Properties ◽

Water Soluble Drugs

The European Medicines Agency (EMA) and the Current Good Manufacturing Practices (cGMP) in the United States of America, define excipient as the constituents of the pharmaceutical form other than the active ingredient, i.e., any component that is intended to furnish pharmacological activity. Although dendrimers do not have a pharmacopoeia monograph and, therefore, cannot be recognized as a pharmaceutical excipient, these nanostructures have received enormous attention from researchers. Due to their unique properties, like the nanoscale uniform size, a high degree of branching, polyvalency, aqueous solubility, internal cavities, and biocompatibility, dendrimers are ideal as active excipients, enhancing the solubility of poorly water-soluble drugs. The fact that the dendrimer’s properties are controllable during their synthesis render them promising agents for drug-delivery applications in several pharmaceutical formulations. Additionally, dendrimers can be used for reducing the drug toxicity and for the enhancement of the drug efficacy. This review aims to discuss the properties that turn dendrimers into pharmaceutical excipients and their potential applications in the pharmaceutical and biomedical fields.

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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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