Solubility Enhancement Techniques Research Articles

Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

Solubility Enhancement of Poorly Water-Soluble Aceclofenac by Amalgamation Micronization and Solid Dispersion Techniques

Aceclofenac is a poorly aqueous soluble Biopharmaceutical Classification System (BCS) class II drug that has bioavailability problems after oral administration due to low aqueous solubility. There are numerous solubility modification approaches and they also have process limitations. Hence, the present research work aims to use two different solubility enhancement techniques (Micronization with Solid dispersion) simultaneously to counter individual limitations of techniques. The micronization technique increases the solubility of pure aceclofenac through increasing particle surface area, but it produces charged micronized material, leading to segregation and clumping of micronized material. Hence, micronized material handling during dosage form manufacturing is quite difficult. In the present research work, aceclofenac material is micronized by air jet mill to produce materials of below 25 μm size ranges. This micronized aceclofenac material is further encapsulated in a solid dispersion technique to produce amorphous aceclofenac materials. Solid dispersion of micronized aceclofenac was prepared by various techniques like physical kneading, solvent evaporation, melting and a combination thereof using different polymers (Polyox 301, HPMC, cetostearyl alcohol and glyceryl behenate). The prepared solid dispersion formulation (SD-31, SD-22, SD-23 and SD-30) exhibited an increase in the dissolution of aceclofenac as compared to pure aceclofenac. Various characterization techniques (Differential scanning calorimetry (DSC), X-ray Diffraction (XRD) and scanning electron microscope (SEM)) also reveal that aceclofenac crystallinity is significantly minimized in Solid dispersion formulation of SD-31, SD-22, SD-23 and SD-30. This selected solid dispersion (SD-31 and SD-22) also exhibited good stability (Photostability and stability at 40°C/75% RH after 3 months).

A Systematic Review of Solubility Enhancement Techniques Used for BCS Class II & IV

Because of their low solubility, pharmaceutical researchers encounter tremendous difficulties in creating sustainable and more soluble drugs (BCS class II). About 40% of oral dosage forms have formulation and development problems due to water insolubility. The rate of dissolving, absorption, distribution, and excretion of an active medicinal substance is determined by its solubility parameters. Based on their solubility, drugs are divided into four kinds under the BCS categorization system. BCS Class II and Class IV drugs have problems with solubility. Increasing both the bioavailability and the solubility of poorly soluble medications can be accomplished in several ways. Some techniques—like solid dispersion, solid complexation, liquisolid, hydrotropy, sonocrystallization, and self-emulsifying techniques—are commonly used for solubility augmentation. Until an orally active medication dissolves in the lining of the stomach and/or intestinal fluids, it cannot pass through the GI tract membrane and enter the bloodstream. Therefore, a medication that is insoluble in water will typically exhibit limited absorption by dissolution, and a medication that is weakly permeabilized via membranes would typically exhibit limited absorption through permeation. Consequently, improving the oral bioavailability of active substances is the focus of two areas of pharmaceutical research: (i) accelerating the process of dissolution and solubility of drugs that are poorly soluble in water, and (ii) accelerating the permeability of poorly permeable drugs.

Formulation and Evaluation of Oral Dispersible Tablet of Poorly Water-Soluble Drug ‘Glimepiride’ by Using Solubility Enhancement Technique

The present study is regarding Glimepiride (GMP) is poorly water-soluble drug. According to the BCS, Glimepiride undergoes Class II - High Permeability and Low Solubility. The objective of the research project is to enhance the solubility of Glimepiride by using solubility enhancement techniques. The endeavor is to improve its solubility by using super disintegrating agent to enhance the ability of disintegration of Oro dispersible tablet. To enhance of solubility of GMP, our select the method i.e. solid dispersion technique because Solid dispersion is an effective way of improving the dissolution rate of poorly water-soluble drugs and hence its bioavailability. The polymers used were PEG 4000 and PEG 6000 for prepared solid dispersions in different ratio by two method i.e. Fusion and solvent evaporation method. The solvent evaporation method is better result of drug for enhancement of solubility. Oral dispersible tablet of Glimepiride was prepared by direct compression method. ODTs of glimepiride by using different super disintegrants such as sodium starch glycolate, cross povidone and croscarmellose sodium. Further, post evaluation parameters like Shape and Color of Tablets, Thickness, hardness, friability, weight variation, Uniformity of Drug Content, In vitro Dissolution Rate Studies and In-vitro disintegration time were also evaluated and the results were discussed.

Ex vivo propofol permeation across nasal mucosa: A proof-of-concept study for outpatient light sedation via nasal route.

Aiming to achieve light sedation via intranasal administration, this study showed that propofol (PPF) did not permeate across the rabbit nasal mucosa ex vivo from its marketed emulsion for injection. Dilution of the emulsion with methyl-β-cyclodextrin in saline solution increased propofol solubility in water and diffusion across the nasal epithelium. Despite these positive effects of the cyclodextrin, the amount of PPF permeated was minimal in 3 h, exceeding the formulation residence time in the nose. These results highlight the key role of formulation and the need for innovation in solubility and transmucosal transport enhancement techniques to optimize drug delivery and therapeutic efficacy.

A Review of Hydrotropic Solubilization Techniques for Enhancing the Bioavailability of Poorly Soluble Drugs.

Hydrotropic solubilization is a technique that can be used to improve the solubility of drugs that are poorly soluble. This technique involves adding a large amount of a second solute, known as a hydrotrope, which increases the aqueous solubility of the poorly soluble drug. Hydrotropes such as sodium citrate, sodium benzoate, and urea have been shown to be effective in enhancing the solubility of poorly soluble drugs. This technique has several advantages over other solubility enhancement techniques, including its cost-effectiveness, eco-friendliness, and the fact that it does not require chemical modification of hydrophobic drugs or the use of organic solvents. Hydrotropic agents are now being used to develop various dosage forms, including solid dispersions, mouth-dissolving tablets, and injections, to improve poorly water-soluble drugs' therapeutic effectiveness and bioavailability. This review paper will provide an overview of hydrotropic solubilization techniques.

Solubility Enhancement of Poorly Water-Soluble Drugs by Solid Dispersion Techniques

The fact that newly discovered API’s (about 90%) or new molecular entity (NME) have little or poor aqueous solubility, causes a significant challenges to the initialization of development and commercialization of dosage form at the manufacturing facility. Poor aqueous solubility of API’s has critical role in drug dissolution or availability of drug at the site of actionor bioavailability, when a dosage form is administered orally. Various techniques are available for the enhancement of solubility but all individual techniques have its own limitations for commercialization. The known Solubility enhancement techniques like Solid dispersions involved the dispersion of poorly soluble drug in a suitable inert carrier at a molecular level and form amorphous and highly soluble compounds. The conversion of compound in to amorphous form or reduction of particle size to its molecular level caused enhanced solubility of poorly soluble by the application of solid dispersion techniques.

Vitamin-E TPGS Based Microemulsion: An Approach for Solubility Enhancement of Poorly Water-Soluble Drugs

Poor aqueous solubility is the primary concern for dissolving new drug substances during early development. Several novel solubility enhancement techniques such as particle size reduction, salt formation, making solid dispersion, complex formation, use of cosolvent techniques, use of surfactants, physical and chemical modification, and PH adjustment using buffering agents have been explored extensively to resolve the issue of poor aqueous solubility of drug substances. Drug delivery in micro and nano-sized formulations is one of the ways to improve the solubility of these drug candidates over the physiological pH range. In recent years, combination methods have also been considered an interesting approach where more than one solubility enhancement technique is used. The present review focuses on the feasible approach for improving the solubility by forming Vitamin E TPGS-based suspension in micro or nano form by particle size reduction. Further, by granulation or spray drying techniques, these suspensions converted to a solid dosage form for oral drug delivery for patient compliance are being explore

A Comprehensive Review on Pharmaceutical Dosage Form

Pharmaceutical liquid dosage forms are the liquid solutions that can be ingested, applied topically, or administered intravenously. These dosage forms are made up of a mixture of active medicines and excipients that produce a quick beginning of action after ingestion and provide the best therapeutic response in a given population. Pharmaceutical liquid dose forms are helpful and efficient for pediatric, elderly, and comatose patients who have difficulty swallowing solid dosage forms such as pills, capsules, and other medications. As a result, pharmaceutical liquid dosage forms are extremely important in the treatment and management of a wide range of disorders around the global. This article covers a wide range of topics related to pharmaceutical liquid dosage forms, including classification, benefits and drawbacks, excipients utilised in pharmaceutical liquid dosage forms, solubility enhancement techniques, and some of the instruments used to improve mixing.

A Review on Different Solubility Enhancement Techniques of Ticagrelor

Ticagrelor is a BCS class IV drug that inhibits platelet action by reversibly binding to the P2Y12 receptor. One of the major challenges faced by the class IV (low solubility, low permeability) drug is the lower dissolution rate leading to low bioavailability. The bioavailability of the marketed formulation of ticagrelor is approximately 36%. Researchers have come up with various techniques to improve the BCS class II and IV drug formulations as an integral part of the development of the pharmaceutical sciences. An increase in solubility can be achieved by various methods such as Salt formation, Complexation, Micronization, Solid Dispersion, altering the pH, Co-solvency, co-crystals, polymeric micelles, etc. A highly efficacious technique is converting a crystalline drug to its amorphous form. An extensive literature search was conducted using various databases like science direct, Taylor and Francis, Springer to extract relevant articles. Keywords like “Ticagrelor”, “low permeability”, “P2Y12 receptor inhibitor” were used for the literature search. Relevant articles were screened and referred for further study. This article discusses the techniques employed to increase the solubility of ticagrelor, thus highlighting the research conducted and reported. The increase in bioavailability of ticagrelor could be seen when formulated as nanoparticles, co-crystals, ticagrelor loaded self-micro emulsifying and nano emulsifying drug delivery system, solid dispersion, etc. the conversion of the crystalline drug into amorphous drug is a highly recommended approach to increase the solubility of ticagrelor which can be seen in cases of co-crystals and solid dispersion formulation.

A Brief Review on Solubility Enhancement Techniques with Drug and Polymer

A Brief Review on Solubility Enhancement Techniques with Drug and Polymer

A Brief Review on Solubility Enhancement Techniques with Drug and Polymer

A Brief Review on Solubility Enhancement Techniques with Drug and Polymer

A Brief Review on Solubility Enhancement Techniques with Drug and Polymer

The process of a solid dissolving in a liquid phase to create a homogenous mixture is known as solubility. A crucial factor in getting the right quantity of drug into the bloodstream to show a pharmacological effect is solubility. The main issue in developing formulations for new chemical entities as well as for the creation of generics is low water solubility. More than 40% of novel chemical entities (NCEs) created in the pharmaceutical sector are essentially water insoluble. For formulation scientists, solubility is a significant challenge. Any medicine that is to be absorbed at the absorption site must be there in solution form. The solubility of pharmaceuticals that are poorly soluble can be improved using a variety of approaches, such as complexation, salt formation, particle size reduction, crystal engineering, salt formation, solid dispersion, and the like. The choice of a solubility-improving technology is influenced by pharmacological properties, absorption sites, and the requirements for the dosage form. This review article’s goal is to improve bioavailability and promote effective absorption.

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization.

Amorphous solid dispersions (ASDs) are among the most popular and widely studied solubility enhancement techniques. Since their inception in the early 1960s, the formulation development of ASDs has undergone tremendous progress. For instance, the method of preparing ASDs evolved from solvent-based approaches to solvent-free methods such as hot melt extrusion and Kinetisol®. The formulation approaches have advanced from employing a single polymeric carrier to multiple carriers with plasticizers to improve the stability and performance of ASDs. Major excipient manufacturers recognized the potential of ASDs and began introducing specialty excipients ideal for formulating ASDs. In addition to traditional techniques such as differential scanning calorimeter (DSC) and X-ray crystallography, recent innovations such as nano-tomography, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray microscopy support a better understanding of the microstructure of ASDs. The purpose of this review is to highlight the recent advancements in the field of ASDs with respect to formulation approaches, methods of preparation, and advanced characterization techniques

Design and development of fast dissolving liquisolid formulation

Various techniques have been employed for the solubility modification of BCS class II drugs. Out of the recent solubility enhancement techniques, Liquisolid technique based on the work of Spireas et al has explored as method that can supplement drug release. Formulations containing Etodolac were developed by dissolving the drug in a non-volatile solvent and then employing the adsorption absorption principle with a carrier and coated material admixture. The post formulation saturation solubility study has highlighted significant modification in solubility of the drug in comparison to pre solubility modification. The Liquisolid formulation then subjected to direct compression for the development of Fast dissolving tablet formulation using two varying concentrations of Sodium Starch Glycolate. The in vitro - in vivo evaluation of research study concludes adaptability and applicability of fast dissolving liquisolid tablet formulation allowing it to overcome barriers associated with the solubility. The optimized formulation found to unveil dissolution along with diffusion from the dosage form by Fickian mechanism. Keywords: Etodolac, Liquisolid, Carrier material, Coating material Fast dissolving tablet, Superdisintegrant.

Introducing novel hybridization technique for solubility enhancement of Bosentan formulation

Bosentan is choice of drug for pulmonary arterial hypertension. It belongs to BCS class-II category. Due to poor solubility in aqueous media, treatment leads to frequent dosing & increasing cost of therapy subsequently. One cannot unseen the shortcomings of commonly existing solubility enhancement techniques such as physical and chemical modifications of the drug, salt formation, solid dispersion, complexation because of the need for sophisticated equipment, decreased yield, incomplete removal of organic solvents, etc. The novel hybridization technique is a fusion of complexation and liquisolid technique. In this research work, Bosentan was complexed with captisol in the first step. In the second step, the complex was dispersed in non-volatile solvent & mixed with the carrier using mortar-pestle followed by the addition of coating material to form a free-flowing powder. It was then compressed into tablets by mixing with other excipients. The formulation was characterized by phase solubility study, DSC, FTIR, and XRD to confirm drug-excipients compatibility, crystallinity etc. The phase solubility study showed ∼28.85 fold increase in solubility. From screening, Avicel PH101 & Parteck SLC 500 as carrier and coating material respectively & PEG-600 as non-volatile solvent were selected. Explotab as super-disintegrant and Pearlitol 100SD as direct compressible excipient were used. Optimization by 32 factorial design gave Bosentan tablet with disintegrate in time of 7–8 min and showed 87.264±0.823% drug release in 30 min higher than marketed tablet i.e. 61.750±1.226%. From the stability study, the Novel hybridization technique was proved as a choice for solubility enhancement.

Evaluation of in vitro Dissolution Profile and Physicochemical Characterization of Polymer Based Formulations of Sparingly Soluble Rosuvastatin

Rosuvastatin (RVT) is a BCS class II antilipidemic crystalline drug, which exhibits low bioavailability due to its very poor aqueous solubility; therefore, it is challenging to develop a proper formulation of RVT. To enhance solubility and bioavailability of this API, an attempt has been made by implementing solid dispersion technique. Solid dispersion (SD) technique is a solubility enhancing technique where one or more active entities are dispersed in an inert medium (matrix or carrier) at solid state. In this study, different ratios of Kollicoat® IR (KIR) and Kollidon® 90F (KF90) polymers were used with API to prepare various formulations by physical mixing (PM) and SD approaches; here solvent evaporation technique was used whereas methanol was used as solvent which was completely evaporated from the homogenously dispersed system by placing in a water-bath at 60-65°C and then in oven for 30 minutes at 50 °C. Among the formulations, RVT-KF90 SD formulations showed the most promising result in in-vitro study in terms of drug release profile (78.04 – 99.21%) in comparison to pure RVT (63.1%) and physical mixing of RVT with those polymers. USP dissolution apparatus type II was used at 37°C ± 0.5°C with 50 rpm to conduct the in-vitro experiment. The experiment also unraveled that the dissolution of RVT improved with increasing the amounts of polymers. Subsequently, stability of the developed formulations was conducted by Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) as well as scanning electron microscopy (SEM). The results obtained from FTIR ensured no involvement of any significant drug-excipient interaction. Moreover, the DSC study signified thermal stability at high temperature. Besides, the SEM micrograph illustrated homogenous distribution of RVT in the polymer and transformation of crystal-like RVT into amorphous formulations. Dhaka Univ. J. Pharm. Sci. 20(2): 199-211, 2021 (December)

Experimental measurement and thermodynamic modeling of solubility of flufenamic acid in different pure solvents

Flufenamic acid (FFA) is a BCS II class drug having low solubility and high permeability in the gastrointestinal tract. The solubility enhancement techniques of BCS II class drugs such as co-crystallization, solid dispersion or fine particle generation by supercritical or liquid antisolvent method require the knowledge of solubility of API in the organic solvent. In the present work, the equilibrium solubility of FFA was determined in methanol, ethanol, 1-propanol and 2-propanol at a temperature ranging from 298 to 318 K. Different models such as the modified Apelblat equation, λh equation, NRTL and Wilson were used to correlate the experimental solubility of FFA in these solvents. The enthalpy of mixing (ΔmH), entropy of mixing (ΔmS) and Gibbs energy of mixing (ΔmG) were computed in the real binary mixture of FFA – solvent to examine the nature of mixing thermodynamically.

Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems.

One of the major impediments to drug development is low aqueous solubility and thus poor bioavailability, which leads to insufficient clinical utility. Around 70–80% of drugs in the discovery pipeline are suffering from poor aqueous solubility and poor bioavailability, which is a major challenge when one has to develop an ocular drug delivery system. The outer lipid layer, pre-corneal, dynamic, and static ocular barriers limit drug availability to the targeted ocular tissues. Biopharmaceutical Classification System (BCS) class II drugs with adequate permeability and limited or no aqueous solubility have been extensively studied for various polymer-based solubility enhancement approaches. The hydrophilic nature of cellulosic polymers and their tunable properties make them the polymers of choice in various solubility-enhancement techniques. This review focuses on various cellulose derivatives, specifically, their role, current status and novel modified cellulosic polymers for enhancing the bioavailability of BCS class II drugs in ocular drug delivery systems.

Recent solubility and dissolution enhancement techniques for repaglinide a BCS class II drug: a review

Repaglinide is an oral blood-glucose-lowering drug used to manage type-2 diabetes mellitus by lowering post-prandial glucose by stimulating insulin secretion from pancreatic beta cells. According to the biopharmaceutical classification system, repaglinide falls under the class II category. For such drugs, limited solubility and poor dissolution rate are the major hurdles to overcome by formulation scientists, as they hinder drug absorption and lead to inadequate therapeutic effects. Therefore, this review aims to discuss in depth the various approaches investigated in the past five years to improve the solubility and dissolution of orally administered repaglinide: namely, solid dispersion, co-amorphous technology, cyclodextrin complexation, phospholipid complexes and polymeric micelles, nanocrystals, nanosuspensions and nanofibers.