Mansoura National University Pharmacy Orientation Lecture 6 PDF

Pharmacy Orientation Lecture 6  Dr. Dr. Walaa E.Abd El Hady Ghada Ahmed El-Emam Lecturer of Pharmaceutics Lecturer of Pharmaceutics [email protected] [email protected] Dr...

Pharmacy Orientation Lecture 6  Dr. Dr. Walaa E.Abd El Hady Ghada Ahmed El-Emam Lecturer of Pharmaceutics Lecturer of Pharmaceutics [email protected] [email protected] Dr/ Randa Hanie Awadeen Lecturer of Pharmaceutics [email protected]  Preformulation  Preformulation testing is the first step in the development of dosage forms.  It can be defined as an investigation of physical and chemical property of a drug substance alone and when combined with excipients.  Physiochemical properties are those that can be determined from in vitro experiments.  Importance of Preformulation 1. To prepare dosage forms with desired quality. 2. To achieve high degree of physiological availability and therapeutic qualities. 3. To develop an optimum dosage form. 4. For targeted drug delivery systems. 5. For patient compliance. 6. To minimize cost of finished product. 7. To minimize errors in formulation of dosage form.  Physicochemical properties Bulk properties  Bulk properties of the solid form such as crystallinity, polymorphism, particle size, powder flow property, and surface characteristics are likely to change during process development.  Crystallinity  The crystal habit describes the outer appearance of crystals (platy, needle, bladed) and internal structure arrangement.  Compounds have several different habits, depending on the environment for growing crystals.  Polymorphism  Polymorphism is the ability of the compound to crystallize as more than one crystalline species with different internal structure.  Formation of different polymorphs depends on solvents, temperature, pressure, rate of cooling.  Polymorphic transitions can also occur during milling, granulating, drying and compressing operations.  Different polymorphs vary in physical properties such as dissolution, solid-state stability, compatibility.  Particle size  Study of particle size give an information about solubility, dissolution rate, absorption.  Particle size and surface area of a solid drug are inversely related to each other.  Powder flow property  The flow properties of a powder will determine the nature of excipients needed to prepare a compressed dosage form (tablet).  This refers mainly to factors such as the ability to process the powder through machines (tablet machine).  Surface characteristics (e.g. Hygroscopicity)  Hygroscopicity is the tendency of a solid to take up water from the atmosphere.  Solubility analysis  Aqueous solubility  Orally administered drug must dissolve in the aqueous fluid of the gastrointestinal tract (GIT) prior to absorption.  Solubility can be improved by addition of co-solvents.  Drug pKa / Ionization at physiological pH  pKa is the dissociation constant of a drug.  The non-ionized substances  lipid soluble  thus dissolve in lipid material of the membrane and transported by passive diffusion.  On the other hand, the ionized substances  lipid insoluble  therefore permeation is slow.  Partition co-efficient  Partition co-efficient is a concentration of drug in oil phase to concentration of drug in aqueous phase. K = C0/Cw where, C0  organic phase concentration Cw  aqueous phase concentration  Following administration, the drug must travel through a variety of membranes to gain access to the target area.  Drug with extremely high partition co-efficient (i.e. very oil-soluble )  readily penetrate the membranes.  While drugs with high aqueous solubility (i.e. water soluble)  can't penetrate the membrane.  Dissolution  To know the gastrointestinal absorption and other physicochemical properties.  The dissolution rate is determined by the rotating disc method. Stability analysis  Drug stability.  Solution phase stability: The effect of pH on stability is important in the development of both oral and parenteral dosage forms. Acid sensitive drugs have to be protected from highly acidic environment of the stomach (gastric acidity) by coating it with suitable polymers.  Solid phase stability: depends on several factors like temperature, pH, humidity, hydrolysis, oxidation.  Compatibility  Problems arise because of the interaction of drugs and preservatives, stabilizers, dyes, and flavors.  It is important for the formulator of a new drug substance to know with which excipients he can work and which he can't. Pharmacy Orientation 20  Q1: Complete the following: 1- The dissolution rate is determined by the ………..method. 2- Crystal habit describes the ……………. and ………………………. 3- ……………..is the tendency of a solid to take up water from the atmosphere. Q2: Give the Scientific term for each: 1- The first step in the development of dosage forms. 2- A concentration of drug in oil phase to concentration of drug in aqueous phase. Mansoura National University, Faculty of Pharmacy, pharmaceutics Department