Bioavailability Enhancement Techniques for Poorly Soluble Drugs: A Review

Bioavailability is defined as the rate and extent of absorption of unchanged drug from its dosage form. The oral bioavailability of drugs with poor solubility and reasonable permeability is limited by the drug dissolution step from drug products. Low aqueous solubility is the major problem encountered with formulation development of new drugs. The article briefly highlights traditional and novel techniques that are used for solubility enhancement of BCS Class II drugs are discussed in this article. The Traditional techniques include use of co-solvents, hydrotrophy, micronization, change in dielectric constant of solvent, amorphous forms, chemical modification of drug, use of surfactants etc. Novel technologies are size reduction technologies, lipid based delivery system, micellar technologies, solid dispersion and many more.

Download Full-text

Insight into Delivery Approaches for Biopharmaceutics Classification System Class II and IV Drugs

Drug Delivery Letters ◽

10.2174/2210303110999200712185109 ◽

2020 ◽

Vol 10 (4) ◽

pp. 255-277

Author(s):

Shashank Chaturvedi ◽

Raghav Mishra

Keyword(s):

Class Ii ◽

Crystal Habit ◽

Extensive Literature ◽

Formulation Development ◽

Particle Size Reduction ◽

Bioavailability Enhancement ◽

Poor Solubility ◽

Biopharmaceutics Classification System Class ◽

Poorly Soluble ◽

Physical And Chemical

: Formulation development of BCS Class II and IV drugs is a challenging task due to their poor solubility and permeability issue. : An extensive literature survey was conducted to explore the relevant pharmaceutical approaches that have been used for solving the issue of poor solubility and permeability in the recent past. : It has been found that a plethora of approaches have been investigated for addressing the issue of poor solubility and or permeability. These include physical modifications (modification of crystal habit, particle size reduction, complexation, polymorphism and drug dispersion in carriers), chemical modifications (salt formation), and formulation modifications (Nanotechnology-based approaches and hydrotropy). : The physical and chemical modification approaches can be effectively used to enhance the solubility and dissolution rate of poorly soluble drugs, but the additional problem of poor permeability has been better addressed by lipid-based drug delivery systems. As the latter presents the drug in the solubilized state, bypass first-pass effects, circumvent the effect of Para-glycoprotein mediated efflux of drugs, hence contributing to overall bioavailability enhancement.

Download Full-text

In vitro and in vivo Evaluation of Ibuprofen Nanosuspensions for Enhanced Oral Bioavailability

Medical Principles and Practice ◽

10.1159/000516299 ◽

2021 ◽

Author(s):

Mohsen Hedaya ◽

Farzana Bandarkar ◽

Aly Nada

Keyword(s):

Particle Size ◽

Tween 80 ◽

Aqueous Solubility ◽

In Vitro Dissolution ◽

In Vivo Evaluation ◽

Poorly Soluble ◽

Extent Of Absorption ◽

Better Than

Introduction: The objectives were to prepare, characterize and in vivo evaluate different ibuprofen (IBU) nanosuspensions prepared by ultra-homogenization, after oral administration to rabbits. Methods: The nanosuspensions produced by ultra-homogenization were tested and compared with a marketed IBU suspension for particle size, in vitro dissolution and in vivo absorption. Five groups of rabbits received orally 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Serial blood samples were obtained after IBU administration. Results: The formulated nanosuspensions showed significant decrease in particle size. Polyvinyl Pyrrolidone K30 (PP) was found to improve IBU aqueous solubility much better than the other tested polymers. Addition of Tween 80 (TW), in equal amount as PP (IBU: PP:TW, 1:2:2 w/w) resulted in much smaller particle size and better dissolution rate. The Cmax achieved were 14.8±1.64, 11.1±1.37, 9.01±0.761, 7.03±1.38 and 3.23±1.03 μg/ml and the tmax were 36±8.2, 39±8.2, 100±17.3, 112±15 and 105±17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension were the highest for nanosuspension> unhomogenized suspension> nanoparticles> untreated IBU suspension. Conclusion: IBU/PP/TW nanosuspensions showed enhanced in vitro dissolution as well as faster rate and higher extent of absorption as indicated from the higher Cmax, shorter tmax and larger AUC. The in vivo data supported the in vitro results. Nanosuspensions prepared by ultra-high-pressure-homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.

Download Full-text

The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability

Pharmaceutics ◽

10.3390/pharmaceutics12050393 ◽

2020 ◽

Vol 12 (5) ◽

pp. 393 ◽

Cited By ~ 3

Author(s):

Jannes van der Merwe ◽

Jan Steenekamp ◽

Dewald Steyn ◽

Josias Hamman

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Aqueous Solubility ◽

Dosage Forms ◽

Oral Dosage ◽

Drug Dissolution ◽

Specific Reference ◽

Dissolution Rates ◽

Bioavailability Enhancement ◽

Poor Solubility

Many active pharmaceutical ingredients (APIs) exhibit poor solubility and low dissolution rates in aqueous environments such as the luminal fluids of the gastrointestinal tract. The oral bioavailability of these compounds is usually very low as a result of their poor solubility properties. In order to improve the bioavailability of these poorly soluble drugs, formulation strategies have been applied as a means to improve their aqueous solubility and dissolution rates. With respect to formulation approaches, excipients can be incorporated in the formulation to assist in the dissolution process of the drug, or specialized dosage forms can be formulated that improve dissolution rate through various mechanisms. This paper provides an overview of selected excipients (e.g., alkalinizing agents, surfactants and sugars) that can be used in formulations to increase the dissolution rate as well as specialized dosage forms such as self-emulsifying delivery systems and formulation techniques such as inclusion complexes and solid dispersions. These formulation approaches are discussed with available examples with specific reference to positive outcomes in terms of drug solubility and bioavailability enhancement.

Download Full-text

Formulation Development and Evaluation of Liposphere of Poor Water Soluble Drug for Hyperlipidemia

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i2.4578 ◽

2021 ◽

Vol 11 (2) ◽

pp. 23-30

Author(s):

Anil Kumar ◽

Umesh K. Jain ◽

Ajay Patel

Keyword(s):

Drug Release ◽

Stearic Acid ◽

Aqueous Solubility ◽

Class Ii ◽

Water Soluble ◽

Fibric Acid Derivative ◽

Formulation Development ◽

Bcs Class Ii ◽

Paraffin Oil

Lipospheres offer a new approach to improve an aqueous solubility of BCS class-II drugs. Simvastatin is a third generation fibric acid derivative belonging to this class, employed clinically as a hypolipidemic agent to lessen the risk caused by atherosclerosis. An attempt was made to improve aqueous solubility of Simvastatin by aid of stearic acid and Paraffin oil. The factorial batches of the Simvastatin lipospheres were formulated by melt dispersion technique using 32 factorial design with variables X1- concentration of stearic acid and X2- concentration of paraffin oil and responses Y1 - % Drug Entrapment (% DE) and Y2 - % Drug Release (% DR). From the surface response graphs the optimized batch was formulated and evaluated for saturation solubility, in-vitro drug release studies. Significant improvement in the aqueous solubility of the drug in the Simvastatin lipospheres supports the applicability of lipospheres as a tool for improving aqueous solubility of the BCS class-II drugs. Keywords: Linospheres; Simvastatin; Drug release; Hyperlipidemic; Drug entrapment.

Download Full-text

Solubility Enhancement of Poorly soluble Drugs by using Novel Techniques : A Comprehensive Review

International Journal of PharmTech Research ◽

10.20902/ijptr.2019.130211 ◽

2020 ◽

Vol 13 (2) ◽

pp. 80-93 ◽

Cited By ~ 1

Author(s):

Abikesh P.K. Mahapatra ◽

Vinod Patil ◽

Ravindra Patil

Keyword(s):

Dissolution Rate ◽

Class Ii ◽

Systemic Circulation ◽

Poorly Soluble Drugs ◽

Formulation Development ◽

Solid Dosage ◽

Bcs Class Ii ◽

Pharmacological Response ◽

Poorly Soluble ◽

Low Solubility

The primary aim of this review was to improve the solubility and Bioavailability of BCS Class-II drugs because of their low solubility and dissolution rate. Solubility is one of the imp parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown. Hence the class- II drugs require enhancement in solubility and dissolution rate in there formulation development particularly in solid dosage form such as in tablet and capsule. So because of this there are several methods and newer emerging technologies have been developed for increasing the solubility as well as Bioavailability of class –II drugs. In this article review on literature on newer techniques or methods as well as recent research on formulation development of class- II drugs was done.

Download Full-text

Formulation and Nanotechnology-Based Approaches for Solubility and Bioavailability Enhancement of Zerumbone

Medicina ◽

10.3390/medicina56110557 ◽

2020 ◽

Vol 56 (11) ◽

pp. 557

Author(s):

Siddharth S. Kesharwani ◽

G. Jayarama Bhat

Keyword(s):

Aqueous Solubility ◽

Clinical Development ◽

World Population ◽

Formulation Development ◽

Volatile Oils ◽

Bioavailability Enhancement ◽

Drug Molecules ◽

Development Pipeline ◽

Traditional Therapies ◽

Poor Absorption

About 40–70% of drug molecules in the clinical development pipeline suffer from one of either low aqueous solubility, poor absorption, or extremely low bioavailability. Approximately 75% of the world population relies on traditional therapies and therefore there has been a growing interest in the utilization of natural compounds. Zerumbone is one such natural compound, classified as a sesquiterpenoid that is extracted from the essential volatile oils of rhizomes from Zingiber zerumbet. It possesses strong antitumor, antioxidant, antimicrobial, and anti-inflammatory activity. However, despite promising preclinical studies demonstrating the therapeutic utility of zerumbone, its clinical development has been limited due to its low aqueous solubility, poor absorption, or associated low bioavailability. Multiple reviews demonstrating the pharmacological effects of zerumbone for various diseases have been published. However, to our knowledge, no review demonstrates the various formulation strategies developed to overcome the biopharmaceutical challenges of zerumbone. The purpose of this review is to provide a comprehensive perspective on zerumbone as a molecule for formulation development. A section related to pharmacokinetics, toxicity, and patents of zerumbone is included. This review provides the importance of developing novel formulations of zerumbone to overcome its biopharmaceutical challenges thereby advance its potential in the treatment of various diseases.

Download Full-text

Use of Nanohybrid Material for Formulation, Development and Evaluation of Pharmaceutical Dosage Form Containing the Low Solubility Active Pharmaceutical Ingredient

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i6-s.3715 ◽

2019 ◽

Vol 9 (6-s) ◽

pp. 34-43

Author(s):

Aparna Nigal ◽

Avinash Darekar ◽

Ravindranath B. Saudagar

Keyword(s):

Electron Microscopy ◽

Guar Gum ◽

Oral Absorption ◽

Drug Dissolution ◽

In Vitro Dissolution ◽

Dissolution Enhancement ◽

Formulation Development ◽

Bioavailability Enhancement ◽

Pharmaceutical Dosage Form ◽

Rosuvastatin Calcium

In oral absorption of a drug, the drug first dissolves and then is absorbed by diffusion through gastrointestinal membranes. The gastrointestinal environment is aqueous in nature and it is well-known that one-third of the drug population is water insoluble. Hence, there is a need for enhancement of the solubility and dissolution of such drugs. In this work, enhancement of the solubility and dissolution of the practically insoluble drug Rosuvastatin Calcium was achieved by formation of nanohybrids using microwave-induced diffusion (MIND), which ultimately leads to bioavailability enhancement. nanohybrids were formed by using natural carriers such as acacia,guar gum and PVP k-30 with the help of microwaves. Selection of carriers was based on their surfactant and wetting properties. Solubility studies were carried out to establish the solubility-enhancing property of the nanohybrids. To support solubility analysis results, dissolution studies (i.e. powder dissolution and in-vitro dissolution) were carried out. The nanohybrids were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy and transmission electron microscopy. It was found that as the concentration of polymer in the composite increased the solubility and dissolution of rosuvastatin calcium were enhanced. The optimised ratio (drug : polymer) for all the composites was found to be 1:4. The novelty of this work is the green and cost-effective way of forming drug nanocomposites with the help of microwave, which can be scaled up to an industrial level. The method gives an immaculate means of solubilisation by generating drug dispersion at the micro and nanoscale level in natural biodegradable stabilising media. Hence, this study demonstrates the use of nanohybrids in solubility and dissolution enhancement. Keywords- BCS Class II, Nanohybrids, Solubilization, Enhancement of solubility, Optimized drug dissolution and drug release.

Download Full-text

Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers

Pharmaceutics ◽

10.3390/pharmaceutics11010001 ◽

2018 ◽

Vol 11 (1) ◽

pp. 1 ◽

Cited By ~ 11

Author(s):

Kanghee Jo ◽

Jae Min Cho ◽

Hyunjoo Lee ◽

Eun Kyung Kim ◽

Hong Chul Kim ◽

...

Keyword(s):

Aqueous Solubility ◽

Drug Dissolution ◽

Dissolution Behavior ◽

X Ray Diffraction ◽

Hydrophobic Property ◽

Scanning Calorimetry ◽

Solid Dosage ◽

Poorly Soluble ◽

Highly Hydrophobic ◽

Hydrophilic Materials

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.

Download Full-text

Improved Dermal and Transdermal Delivery of Curcumin with SmartFilms and Nanocrystals

Molecules ◽

10.3390/molecules26061633 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1633

Author(s):

Ralph W. Eckert ◽

Sabrina Wiemann ◽

Cornelia M. Keck

Keyword(s):

Drug Delivery ◽

Transdermal Delivery ◽

Aqueous Solubility ◽

Local Concentration ◽

Active Compounds ◽

Drug Products ◽

Dermal Penetration ◽

Penetration Mechanism ◽

Poorly Soluble ◽

Transdermal Penetration

Poor aqueous solubility of active compounds is a major issue in today’s drug delivery. In this study the smartFilm-technology was exploited to improve the dermal penetration efficacy of a poorly soluble active compound (curcumin). Results were compared to the dermal penetration efficacy of curcumin from curcumin bulk suspensions and nanocrystals, respectively. The smartFilms enabled an effective dermal and transdermal penetration of curcumin, whereas curcumin bulk- and nanosuspensions were less efficient when the curcumin content was similar to the curcumin content in the smartFilms. Interestingly, it was found that increasing numbers of curcumin particles within the suspensions increased the passive dermal penetration of curcumin. The effect is caused by an aqueous meniscus that is created between particle and skin if the dispersion medium evaporates. The connecting liquid meniscus causes a local swelling of the stratum corneum and maintains a high local concentration gradient between drug particles and skin. Thus, leading to a high local passive dermal penetration of curcumin. The findings suggest a new dermal penetration mechanism for active compounds from nano-particulate drug delivery systems, which can be the base for the development of topical drug products with improved penetration efficacy in the future.

Download Full-text

Recent Advances in Self-Emulsifying Drug Delivery Systems

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2015.8.1.1 ◽

2015 ◽

Vol 8 (1) ◽

pp. 2693-2697

Author(s):

Amol S Deshmukh

Keyword(s):

Drug Delivery ◽

Drug Delivery Systems ◽

Aqueous Solubility ◽

Oral Route ◽

Delivery Systems ◽

Novel Technologies ◽

Oral Formulations ◽

Modern Drug ◽

New Chemical Entities ◽

Poorly Soluble

Oral route has always been preferred route for formulators and has dominated over other routes of administrations. But major problem encountered in oral formulations (as estimated more than 50 % of oral formulations are found to be poorly aqueous soluble), is low bioavailability, giving rise to further problems like, high inter and intra subject variability, lack of dose uniformity and finally leading to therapeutic failure. Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. Particularly for BCS class II substances, the bioavailability may be enhanced by increasing the solubility and dissolution rate of the drug in the gastro-intestinal fluids. The newer and novel technologies developed in recent year for troubleshooting such above problems. This review describes an overview of SEDDS as a capable approach to effectively capture the problem of poorly soluble molecules and give the novel approaches for evaluation of the SEDDS. Self-emulsifying drug delivery systems (SEDDS) are isotropic mixtures of drug, lipids and surfactants, usually with one or more hydrophilic co-solvents or co-emulsifiers.

Download Full-text