The partition coefficient, abbreviated p, is defined as a particular ratio of the concentrations of a solute between the two solvents a biphase of liquid phases, specifically for unionized solutes, and the logarithm of the ratio is thus log p 275ff when one of the solvents is water and the other is a nonpolar solvent, then the log p value is a measure of lipophilicity or hydrophobicity. Partition coefficient partition coefficient of metoprolol succinate was determined by dissolving the 10 mg drug in 10 ml mixture of noctanol and 6. Determining partition coefficient log p, distribution coefficient log d and ionization constant pka in early drug discovery authors. Pdf solubility, ionization and lipophilicity of a drug molecule are known to. The geochemical parameters most likely to influence the partition coefficient were entered in the spreadsheet along with reported or calculated coefficients if such were specified in the. The main purpose of the preformulation is to generate useful information for the development of a pharmaceutical dosage form formulation. In contrast, for ionic compounds, the distribution constant, which accounts for partitioning of both charged and noncharged species, is phdependent and can be measured at various ph. Effects of salinity, ph and temperature on the octanol. Solubility, dissociation or ionization constant, partition coefficient in preformulation free download as powerpoint presentation. Physicochemical properties of api impact on formulation. Preformulation studies for the development of a parenteral. Solubility study, partition coefficient determination, uv analysis, hplc study, ftir study were also performed. Second edition pharmaceutical preformulation and formulation. This ratio is known as the partitioncoefficient,or distribution coefficient, and is essentially independent of concentration of dilute solutions of a given solute species.
Partition coefficient oxygen evolution rate algae trimecaine chlorella vulgaris the understanding of a number of biological processes requires the knowledge of partition coefficients k p. The physicochemical evaluation as part of preformulation studies of the recieved drug. Partition coefficient significances how and what extent the drug will dissociate and then cross the cellular barrier to what extent of absorption. Fundamentals and physical chemistry, 1997, 170 pages, j.
Partition coefficient determination the partition coefficient is defined as the ratio of unionized drug distributed between the organic and aqueous phase at equilibrium. Like partition coefficient, dissociation constant pka is the property that determines the solubility in phdependent environment and extent of ionization. These metrics are regularly updated to reflect usage leading up to the last few days. Preformulation perspective solid drug drug in solution hydrolysis into active general circulation hydrolysis absorption waste dissolution precipitation 35% 9597% dosage form design. Physicochemical properties of api impact on formulation development duk soon choi, ph.
Solubility, pka and octanolwater partition coefficient were determined by uv. Determining partition coefficient log p, distribution. A simple method of determination of partition coefficient. Bharate, preformulation laboratory, csirindian institute of integrative medicine, canal road, jammu180001, india, india vikas kumar, ram a. The method allows the determination of partition coefficients for biological objects such as algae, bacteria and other microorganisms. The kow represents the membrane lipidwater barrier because octanol c7h15ch2oh represents lipids in living organisms due to the similar carbon to oxygen ratio. Preformulation studies of efda, a novel nucleoside reverse. Three solubility models which alternatively utilize both octanolwater partition coefficients and hprplc retention times as predictors of the saturationlimit aqueous activity coefficient will also be compared. The gastrointestinal membranes are largely lipoidal in character hence the lipid solubility of a drug is an imp. The aim of this work was to provide preformulation information of efda important for delivery system development. Partition coefficient weak acid partial molal volume centrifugal partition chromatography immiscible liquid phasis these keywords were added by machine and not by the authors. Introduction the poor aqueous solubility of sqv can limit its gastrointestinal absorption which, together with other physicochemical properties, reduces oral bioavailability. Preformulation consists essentially in the study of physicochemical properties of the drug as a first step in the pharmaceutical developing of a drug substance 1,2. Ahuja,1 st edition,20042005 polymorphism in pharmaceutical sciences.
Determination of coefficient of apparent gsh of freeze dried samples the determination of the apparent coefficient is performed as in the equilibrium timing. Office of radiation and indoor air office of solid waste and emergency response. An overview on preformulation for pharmaceutical product. Ionization and solubility parameters were assessed prior to formulation development. Solubility, dissociation or ionization constant, partition. Preformulation is the stage of development during which the physicochemical properties are characterized by some parameters some of these include solubility, dissolution behavior, stability, partition coefficient, ionization constant, solid statestate properties such as crystal form, water sorption. Various organic solvents used in determination of partition coefficient include chloroform, ether, amyl acetate, etc. Our scientists have the expertise to link the information generated at this stage to. Importance of partition coefficient in formulation development.
The drug molecule must be unionised in aqueous solution. Derived preformulation properties are specific to the intended dosage form to be developed. Preformulation each type of dosages forms requires careful study of the physical and chemical properties of drug substances to achieve stable, efficious product. In formulation development the noctanolwater partition coefficient is commonly used. Various organic solvents are used in the determination of partition coefficient include chloroform, ether, amyl acetate etc. Preformulation laboratory, csirindian institute of integrative medicine, canal road, jammu180001, india, medicinal chemistry division, csirindian institute of. Understanding variation in partition coefficient, k d, values volume ii. Partition coefficient formula definition and examples. The octanolwater partition coefficient is recognized by. Thus in formulation development the noctanolwater partition coefficient is commonly used. Introduction disadventages of uv radiation, either directly or indirectly. Our scientists have the expertise to link the information generated at this stage to develop a quality product. Preformulation parameters characterization to design. The partition coefficient the lipophilicity of an organic compound is usually described in terms of a partition coefficient, log p, which can be defined as the ratio of the concentration of the unionized compound, at equilibrium, between organic and aqueous phases.
Uv damage which is estimated to occur about 50% due to free radical formation. Preformulation study, saquinavir, ph, spectrophotometry, partition coefficient 1. It is defined as the ratio of unionised drug distributed between the organic and aqueous phases at equilibrium. The overall objective of preformulation studies is to generate information useful in developing stable and bioavailable and sustained release dosage forms which can be mass produced. Pdf pharmaceutical preformulation studies in formulation. If a third substance, which is soluble in both liquids, is added into the system it is found to distribute, or divide, itself between the two layers in a definite manner. Sometimes a value is calculated from knowledge of the molecular structure rather that determined experimentally. Importance of partition coefficient, solubility and. It is the extent of ionization that determines the absorption as only unionized form can be absorbed and hence it becomes essential to determine the pka value of molecule.
Partition coefficient and glutathione penetration of topical. Partition coefficient and glutathione penetration of. Fundamental preformulation properties include solubility, dissociation constant pka, salt formation, partition or distribution coefficient. The value of the apparent partition coefficient can. The media can be gases such as air, liquids such as water or olive oil, or complex mixtures such as blood or other tissues. Key wordsorganic pollutants, soilsediment sorption, bioconcentration, activity coefficient, solubility, octanolwater partition coefficient, high performance reverse phase liquid chromatography nomenclature roman symbols a and c regression coefficients correlating reten tion times and octanolwater partition. Review of geochemistry and available k d values for cadmium, cesium, chromium, lead, plutonium, radon, strontium, thorium, tritium 3 h, and uranium august 1999 a cooperative effort by. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. Research article preformulation studies and preperation of. General considerations of design and development of dosage. For unionised drug p concentration of drug in octanolconcentration of drug in water for. Chapter 1 preformulation studies rsc publishing doi. The preformulation studies were carried out in terms of testa for identification physical appearance, melting point, and uv spectrophotometer, solubility profile, determination of partition coefficient and quantitative estimation of drug.
The partition coefficient can be defined as the partition of a neutral noncharged species into a lipid phase, a process that is not phdependent ku et al. Peldesine bcx34 is a potent inhibitor of the enzyme purine nucleoside phosphorylase pnp. A partition coefficient is simply the ratio of the concentration of anesthetic in one phase or solvent compared to another. Exercise 2 partition coefficient of succinic acid theory consider a system consisting of two liquid layers phases of two immiscible or partiallly miscible liquids. Determining partition coefficient log p, distribution coefficient log d and ionization constant pka in early drug discovery volume. Partition coefficient formula partition coefficients are described as the concentration ratio of a chemical amidst the two media at equilibrium. The object of this study was to determine the preformulation parameters of bcx34 and subsequently prepare a sterile liquid formulation for intravenous infusion. The partition coefficient was determined by formula. Pow c oil c water equilibrium partition coefficient is a measure of drugs lipophilicity and an indication of its ability to cross biomembrane. Polymorphism having crystal and amorphous forms shows different chemical physical and therapeutic description of the drug molecule. The partition coefficient is commonly determined using an oil phase of octanol or chloroform and water. Preformulation study, intrinsic solubility, partition coefficient, compatibility study. Drugs having values if p much greater than 1 are classified as lipophilic, whereas those with partition coefficient much less than 1 are indicative of a hydrophilic drug. Partition coefficients and other data from the articles were then entered into an excel 97 spreadsheet for compilation and analysis.
Of solubility, dissociation or ionization constant, partition coefficient in preformulation definition of solubility solubility is the mass of solute that dissolves in a specific mass or volume of solvent at a given temperature. Pow c oil c water equilibrium partition coefficient is a measure of drugs lipophilicity and an. Citations are the number of other articles citing this article, calculated by crossref and updated daily. Preformulation studies were performed to check the compatibility of drug and excepient for the preparation of formulation by dsc and no interaction was found. The coefficients of most clinical relevance are the blood.
Introduction preformulation study is the foundation of developing robust formulation. The partition coefficient, kp, quantifies the equi librium partitioning of a liquid or supercooled organic solute between two phases k cc where ci and c are the molar concentrations of solute i in phases x and y, respectively. This process is experimental and the keywords may be updated as the learning algorithm improves. Preformulation studies the formulation development centre at syngene offers a wide range of services for pre formulation studies to support formulation and process development.
Experimental determination of the octanolwater partition. The formulation development centre at syngene offers a wide range of services for pre formulation studies to support formulation and process development. Partition coefficient an overview sciencedirect topics. Among these properties, drug solubility, partition coefficient, dissolution rate, polymorphic forms and stability are plays important role in preformulation study. The octanolwater partition coefficient kow is the equilibrium ratio of concentration of a dissolved chemical between octanol and water at a specified temperature 9. Partition coefficient is a measure of a drugs lipophilicity and an indication of its ability to cross the cell membrane. A simple method of determination of partition coefficient for. Since drug absorption depends on the chemical nature of the drug molecule as well as the absorption site media ph and other buffering environment. When one of the solvents is water and the other is a nonpolar solvent, then the log p value is a. Preformulation for the achieving goals of drug and dosage forms, preformulation testing is a first step in the development of dosage forms before the formulation. Log p values have been studied in approximately 100 organic liquidwater systems. The octanolwater partition coefficient is a laboratorymeasured property of a substance. Even when a drug substance is readily soluble at physiological phs, its ability to transfer across membranes can be highly dependent on. Partition coefficients are used extensively in chemical and environmental engineering to determine the behavior and fate of chemicals.