preformulation Xiaohui Wei xhwei@sjtu.edu.cn 2008.9
preformulation preformulation Xiaohui Wei xhwei@sjtu.edu.cn 2008.9
Preformulation Objective: Preformulation involves the application of biopharmaceutical principles to the physicochemical parameters of a drug with the goal of designing an optimum drug delivery system.Characterization of drug molecule is a very important step at the preformulation phase of product development. From www.pharmquest.com
Preformulation Objective: Objective: Preformulation Preformulation involves the application of involves the application of biopharmaceutical principles biopharmaceutical principles to the physicochemical physicochemical parameters parameters of a drug with the goal of designing an of a drug with the goal of designing an optimum drug delivery system. optimum drug delivery system. Characterization of drug Characterization of drug molecule is a very important step at the molecule is a very important step at the preformulation preformulation phase of product development. phase of product development. From www.pharmquest.com
Preformulation Studies:contents Physicochemical properties of the drug 。Solubility 。pKa .Partition Coefficient (lipophilic vs.hydrophilic) .Crystal Properties and Polymorphism Particle size,shape and surface area 。Hygroscopicity Stability 。Chemical stability In solid state In solution phase Compatibility Stability in the presence of excipient Biopharmaceutics research
Preformulation Preformulation Studies: contents Studies: contents Physicochemical properties of the drug Physicochemical properties of the drug z Solubility z pKa z Partition Coefficient ( Partition Coefficient (lipophilic lipophilic vs. hydrophilic) vs. hydrophilic) z Crystal Properties and Polymorphism z Particle size, shape and surface area z Hygroscopicity Stability Stability z Chemical stability Chemical stability z In solid state & In solution phase In solid state & In solution phase Compatibility Compatibility z Stability in the presence of excipient Biopharmaceutics Biopharmaceutics research research
1.Physicochemical properties of the drug 1.1.SOLUBILITY 1.Significance Intrinsic solubility (Co dissociation constant(pKa) Co will immediately indicate need and pKa possibility of making more soluble form (salt)of the drug to eliminate solubility-related poor bioavailability,particularly with solid dosage form. Kaplan(1972):37 C,pH1-7,solubility<1%(10mq/ml). absorption problem,dissolution-limited absorption
1. Physicochemical properties of the drug Physicochemical properties of the drug 1.1. SOLUBILITY 1.1. SOLUBILITY 1.Significance 1.Significance z Intrinsic solubility (C0) z dissociation constant (pKa) C0 will immediately indicate will immediately indicate need and pKa possibility possibility of making more soluble form (salt) of the drug to eliminate making more soluble form (salt) of the drug to eliminate solubility solubility-related poor bioavailability, particularly with related poor bioavailability, particularly with solid dosage form solid dosage form. Kaplan(1972): 37 Kaplan(1972): 37℃, pH1-7, solubility<1%(10mg/ml), solubility<1%(10mg/ml), absorption problem, dissolution absorption problem, dissolution-limited absorption limited absorption
Solubility Definition: Solubility is generally expressed as the maximum amount of solute that dissolves in a given volume of solvent. As water is the most used solvent in pharmacy and biological fluids are aqueous solutions,we will focus on solubility in water. Saturated Solution: A solution where the dissolved solute is in equilibrium with the undissolved solute( the solid phase) Solubility(Cs上z The concentration of a solute in saturated solution at a given temperature and pressure
Solubility Definition: Solubility is generally expressed as the maximum amount of solute that dissolves in a given volume of solvent. As water is the most used solvent in pharmacy and biological fluids are aqueous solutions, we will focus on solubility in water. Saturated Solution: A solution where the dissolved solute is in equilibrium with the undissolved solute( the solid phase) Solubility(Cs): The concentration of a solute in saturated solution at a given temperature and pressure