Reddy LH, Ghosh B. Fast dissolving drug delivery systems: A review of the literature.
Water-Insoluble Drug Formulation, Second Edition ebook
Indian J Pharm Sci ; Fast dissolving drug delivery systems; a brief overview. Internet J Pharmacol ; Maheshwari RK, Indurkhya A. Formulation and evaluation of aceclofenac injection made by mixed hydrotropic solubilization technique. Iran J Pharm Res ; Enhancement of solubility of fenofibrate by using different solubilization techniques.
Asian J Pharm Life Sci ; Maheshwari RK, Jagwani Y.
Water-Insoluble Drug Formulation, Second Edition pdf free
Mixed hydrotropy: Novel science of solubility enhancement. Jayakumar C, Morais AP. Solubility enhancement of theophylline drug using different solubilization techniques. Int J Pharm Pharm Sci ; Mouth dissolving tablets of salbutamol sulphate: A novel drug delivery system.
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The Theory and Practice of Industrial Pharmacy. New Delhi: Varghese Publishing House; Rapidly disintegrating oral tablets of meloxicam. Preparation and evaluation mouth dissolving tablets of salbutamol sulphate.
Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull Tokyo ; MC Clure N. Stability studies in overview of ICH guidelines for drug products. Choonara,Lisa C. Londhe,Aishwarya B.
Water-Insoluble Drug Formulation / Edition 2
Deshmane,Sarita R. Co-solvents used in lipid-based formulations include propylene glycol, ethanol, PEG, glycerol, and diethylene glycol monoethyl ether. Possible combinations for lipid-based formulations thus approach an endless number, but a consideration of the structure and physical-chemical properties of the drug candidate may allow one to narrow the search.
Less hydrophobic drugs viz. Often a combination of low HLB and high HLB surfactants give superior solubilization, which may also optimize the dispersion properties described later. Screening studies can be carried by mixing the required drug amount in the formulation and examining visually or microscopically for the presence of drug crystals, followed by more accurate determination of solubility values of drug in the most promising formulations by HPLC.
High throughput screening systems have been employed to increase efficiency.
Statistical and experimental design studies, such as a simplex lattice mixture or a central composite design, have also been used to optimize and develop SMEDDS formulations of celecoxib  and bufalin , respectively. Nevertheless, as pointed out in the review by Rane and Anderson , prediction of drug solubility in lipid vehicles is difficult due to the dominant role played by interfacial effects and the possible presence of complex microstructures.
While it is difficult to predict optimal formulations based solely on physicochemical properties of the candidate, some progress has been made.
Thi et al. Frequently, toxicology studies will have been carried out with waterinsoluble drug candidates in lipid vehicles. Constraints may be different for the two situations; safety requirements of excipients will be more stringent for clinical formulations, but doses will likely be lower. Nevertheless, toxicology vehicles for a given drug may provide a starting point for development of a First-in-Human and subsequent formulations.
Figure 1 - Ternary phase diagram of an oil-surfactant water system, based on a C12Eoleic acid-water system. Adapted from reference 4.
Water-Insoluble Drug Formulation
Formulations that exhibit sufficient solubility of the drug candidate should be examined for emulsification and dispersion properties in aqueous vehicles. A preliminary screen can be carried out by microscopic observation of the formulation when mixed with water. Absence of drug precipitate after complete mixing of the formulation with aqueous medium is another requirement.
Particle size measurement of emulsion droplets by laser light scattering or other techniques is useful to select promising formulations. Construction of ternary phase diagrams is a method frequently used to determine the types of structures resulting from emulsification and to characterize behavior of a formulation along a dilution path.
It is often unnecessary to construct the entire phase diagram, but an understanding of the structures arising on a dilution path of a given formulation is important to assure formation of stable dispersed structures upon dilution. Appropriate combinations of low HLB and high HLB surfactants frequently lead to smaller emulsion droplet size than single surfactants. Dispersion properties can be examined and optimized as part of an experimental design study.
Droplet size after dilution, turbidity, and dissolution percentage of drug after 5 minutes and 30 minutes were the variables examined to optimize a formulation consisting of glyceryl monolinoleate, medium chain triglyceride, polyoxyl 35 castor oil, caprylocaproyl macrogolglyceride, and diethylene glycol monoethyl ether . The optimal formulation was polyoxyl 35 castor oil, polysorbate 80, acidified PEG, and propylene glycol monocaprylate .
The same type of design was used to optimize a SEDDS formulation of lacidipine, with droplet size, optical clarity, drug release, and emulsification efficiency as the factors examined. Ideally, drug solubility and dispersion should be examined together. While presence of a co-solvent may enhance solubility of the drug in the dosage form, high amounts of hydrophilic co-solvent may lead to drug precipitation after dispersion due to diffusion of the co-solvent away from the emulsion droplet into the bulk aqueous phase. Mohsin et al. If sufficient amounts of lipid medium chain triglyceride were present, formation of supersaturated systems sometimes resulted which nevertheless retarded precipitation for adequate time .
Experimental design studies examining both drug solubility and dispersion properties can aid in identifying formulations with optimal behavior with respect to both factors. For example, a simplex lattice experimental design approach was used to optimize SEDDS formulations of curcumin based on ethyl oleate, PEG, and polyoxyl 35 castor oil . The actions of intestinal lipases can have a profound effect on the behavior of lipid-based formulations in the GI tract, and must be considered in their design.
Thus, the presence of high amounts of surfactants may be unnecessary to assure creation of the requisite small particle sizes and large surface areas for drug release. In , Pouton proposed a classification system for lipid-based formulations based on the formulation components and the dependence on digestion to facilitate dispersion ; this is shown in Table 2. Proshin , Irina Vladimirovna Terekhova. Cyclodextrin: a promising candidate in enhancing oral bioavailability of poorly water soluble drugs Pankaj M Maheriya.
Formulation and characterization of an apigenin-phospholipid phytosome APLC for improved solubility, in vivo bioavailability, and antioxidant potential. Darshan R. Telange , Arun T. Self-emulsifying preconcentrates of daidzein-phospholipid complex: design, in vitro and in vivo appraisal.
Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles Prachi B.
Shekhawat , Varsha B. References Publications referenced by this paper. Pharmacosomes: the lipid based novel drug delivery system.