Solubility

The solubility of a substance becomes especially important in the pharmaceutical field because it often represents a major factor that controls the bioavailability of a drug substance. Moreover, solubility and solubility-related properties can also provide important information regarding the structure of drug substances, and in their range of possible intermolecular interactions. For these reasons, a comprehensive knowledge of solubility phenomena permits pharmaceutical scientists to develop an optimal understanding of a drug substance, to determine the ultimate form of the drug substance, and to yield information essential to the development and processing of its dosage forms.

The objective was to enhance the solubility and dissolution rate of Artemether poorly water soluble antimalarial, by the preparation of solid dispersion (SD) granules. The dispersion granules were prepared using a hot melt granulation technique which involved the preparation of a homogenous dispersion of ARTM in surfactant melt, followed by its adsorption onto the surface of AEROPERL® 300 Pharma, an inert absorbent using the solvent evaporation method. The dispersion granules were characterized for their in-vitro dissolution rate, moisture content and flow properties. The formulation was further characterized by FTIR,DSC, XRD and SEM analysis. FTIR spectrum revealed some drug excipient interactions. DSC and XRD data indicated the retention of amorphous form of ARTM. SEM confirmed the homogeneity and surface adsorption of the ARTM-Lutrol F127 or ARTM-Lutrol F68 melt on AEROPERL® 300 Pharma leading to an enhanced surface area and thus the dissolution rate. The optimized dispersion granules were filled inside the capsules and evaluated. The in-vitro dissolution rate of these capsules was significantly better in comparison with pure drug. Physical characterisation enabled us to understand the effects of formulation variables on the dispersion granules of ARTM.

Poor water solubility has always been one of the most fundamental problem in drug delivery. It is estimated that around 40% of drugs in the pipeline cannot be delivered through the preferred route or in some cases, at all owing to poor water solubility. Different methods available to improve solubility and dissolution include salt formation, micronization, chemical modification, pH adjustment, solid dispersion, complexation, hydrotropy, micellar solubilisation. Among these, solid dispersions have proved to be a successful strategy for enhancing aqueous solubility of drugs. The present review focus on different solid dispersion techniques used for the improvement of solubility and dissolution rate of poorly water soluble drugs, carriers used, advantages and limitations of each technique.

The objective of this study was to develop self-emulsifying drug delivery system (SEDDS) to enhance the solubility of the poorly water-soluble drug Orlistat. Orlistat is class II molecule according to BCS (Biopharmaceutical Classification System), having low solubility and low permeability. The rate and extent of absorption of class II compounds is highly dependent on the performance of the formulated product. These drugs can be successfully formulated for oral administration, but care needs to be taken with formulation design to ensure consistent bioavailability. Solubility of Orlistat was evaluated in various nonaqueous carriers that included oils, surfactants, and cosurfactants. Pseudoternary phase diagrams were constructed to identify the self-microemulsification region. Self microemulsifying formulations were prepared using mixtures of oils, surfactants, and cosurfactants in various proportions. The self microemulsification properties, droplet size and thermodynamic stability of these formulations were studied upon dilution with water. The optimized liquid SMEDDS formulation was converted into free flowing powder by adsorbing onto a solid carrier for encapsulation. The dissolution characteristics of solid intermediates of SMEDDS filled into hard gelatin capsules were investigated and compared with pure drug and commercial formulation. The results indicated that solid intermediates showed the rate and extent of drug dissolution for solid intermediates were significantly higher than commercial formulation. The results of the study demonstrated the potential use of SMEDDS as a means of improving solubility, dissolution and concomitantly the bioavailability.

The aim of this study is to enhance the solubility of poorly water soluble drugs via the mixed hydrotrophic solid dispersion strategy using ibuprofen as a model drug because Ibuprofen is absorbed after oral administration, it is critical to improve the dissolution rate to enhance the bioavailability, due to its low water solubility. Solid dispersions were prepared by mixed hydrotrphic method. In vitro dissolution studies showed remarkable improvement in solubility and drug dissolution profile of these new ibupro­fen solid dispersions over pure ibuprofen. It was observed that dissolution rate of ibuprofen enhanced to a great extent by solid dispersion technique using citric acid and urea as a hydrotrophic agents.The results indicates that mixed hydrotrophic solid dispersion may serve as a successful strategy for enhancing solubility of poorly water soluble drugs.

  Self Micro-emulsifying drug delivery systems (SMEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Approximately 60-70% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. SMEDDS is isotropic (one phase system) mixture of oil or modified oils, surfactants and co-surfactants, which form the fine oil-in-water microemulsion when introduced into aqueous phase under condition of gentle agitation. The digestive motility of the stomach and intestine provide the agitation necessary for self-microemulsion in-vivo. Triglyceride is the one of the component of SMEDDS, which helps in the absorption of drugs from the GI tract. SMEDDS enhance the bioavailability enabling reduction in dose of the drug. SMEDDS is evaluated by various methods like visual assessment, droplet polarity and droplet size, size of emulsion droplet, dissolution test, charge of oil droplets, viscosity determination, in-vitro diffusion study. This article gives an overview of improvement in the rate and extent of oral absorption of drugs by SMEDDS approach. The characterization of SMEDDS and application of SMEDDS is also introduced, with particular emphasis being placed on the developments of Solid self micro-emulsifying delivery system and dosage form of SMEDDS.

Domperidone is a water insoluble drug exhibiting poor dissolution pattern. Domperidone is an antiemetic and shows gastroprokinetic properties. It is a weak base and shows poor solubility in alkaline pH. Several methods are being employed to enhance the solubility of domperidone irrespective of its pH dependent solubility. The present protocol aim to design Polyethylene glycol (PEG) based solid dispersions of Domperidone to enhance its solubility. PEG 8000 based solid dispersions containing the drug in different mass ratio i.e. 1:1, 1:3, 1:5 and 1:7 were prepared using fusion method. The prepared solid dispersions were characterized for their drug content, phase solubility studies, Fourier-transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), x-ray diffraction, and in-vitro dissolution studies. All the formulations showed marked improvement in the solubility and dissolution rate of drug which may be due to decrease in crystallinity of drug and additives. It was concluded that prepared solid dispersion of the Domperidone with PEG can improve the solubility and dissolution rate of the drug.

  Rosiglitazone is a poorly water-soluble (BCS class II) antidiabetic drug. Due to the poor water solubility of this drug, its bioavailability is dissolution rate-limited. The purpose of this study was is to increase the solubility of Rosiglitazone (RG) in aqueous media by solid dispersion (SD) technique with Poloxamer (PXM) 188 and Poloxamer (PXM) 407 by using the kneading method. The RG-PXM solid dispersion system was characterized by Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) analysis, Fourier transform-infrared spectroscopy (FT-IR) and Scanning electron microscopy (SEM), and in vitro dissolution studies. No chemical interaction was found between RG and PXM 188 or PXM 407. The results from DSC, XRD and SEM studies show that PXM 188 or PXM 407 inhibits the crystallization of RG. The SDs prepared in this study were found to have better dissolution rates in comparison to intact RG and physical mixture of PXM 188 or PXM 407. It was found that the optimum weight ratio for drug: Carrier is 1:5 for PXM 188 and 1:6 for PXM 407. Key-Words: Solubility, Rosiglitazone, Solid dispersion

The term “liquisolid medication” implies oily liquid drugs and solutions or suspensions of water insoluble drugs carried in suitable non-volatile solvent systems. Liquisolid compacts demonstrated a considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets. This was due to the increased wetting properties and surface of drug available for dissolution. This review paper highlights the application of liquisolid technique to enhance the solubility and dissolution of water insoluble drugs. This technique is appropriate for poorly or water insoluble drugs and also for immediate or sustained release formulations. This review also depicts the various formulation parameters that must be optimized before formulation the liquisolid compacts.