Pharmacy Orientation Lec 2 Factors Affecting Drug Dosage PDF

Mansoura University Faculty of Pharmacy Dept. of Pharmaceutics Pharm D Program Pharmacy Orientation Pt 111 Dr. Mariza Fouad Farag Boughdady Associate Professor of pharma...

Mansoura University Faculty of Pharmacy Dept. of Pharmaceutics Pharm D Program Pharmacy Orientation Pt 111 Dr. Mariza Fouad Farag Boughdady Associate Professor of pharmaceutics Faculty of pharmacy Mansoura University Pharmacy Orientation 1  Course Contents Topics Credit Hours Mission of Pharmacy √ 1 The Pharmacy Career 2 Factors Affecting Drug Dosage 1 General Dispensing Procedures 1 Routes of drug administration 1 The Prescription 2 Pharmaceutical Dosage Forms 3 Classification of Medications (self-learning). 1 Source of Drugs (self-learning). 1 ‫تاريخ الصيدلة‬ 1 13 hours 2 Pharmacy Orientation  3 Pharmacy Orientation Factors Affecting Drug Dosage 4 Pharmacy Orientation  Preformulation testing is the first step in the rational development of dosage forms. It can be defined as an investigation of physical and chemical properties of a drug substance alone and when combined with excipients. Physiochemical properties are those that can be determined from in vitro experiments. These properties determine many of the subsequent events and approaches in formulation development. 5 Pharmacy Orientation To prepare dosage forms with desired quality. To achieve high degree of uniformity, physiological availability and therapeutic qualities. To develop an optimum dosage form. For targeted drug delivery systems. For patient compliance. To minimize cost of finished product. To minimize errors in formulation of dosage form. 6 Pharmacy Orientation  01 Bulk properties Solubility analysis 02 03 Dissolution Stability analysis 04 7 Pharmacy Orientation  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. 8 Pharmacy Orientation  Crystallinity The crystal habit describes the outer appearance of crystals (platy, needle, bladed,..etc.) and internal structure arrangement. Compounds have several different habits, depending on the environment for growing crystals. 9 Pharmacy Orientation  Polymorphism Polymorphism: is the ability of the compound to crystallize as more than one distinct crystalline species with different internal structure. Formation of different polymorphs depends on solvents, temperature, pressure, rate of cooling,.....etc. 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,.....etc. 10 Pharmacy Orientation  Particle size Study of particle size give an information about solubility, dissolution rate, absorption,....etc. Particle size and surface area of a solid drug are inversely related to each other. 11 Pharmacy Orientation  Powder flow property The flow properties of a powder will determine the nature and quantity of excipients needed to prepare a compressed or a powder dosage form. This refers mainly to factors such as the ability to process the powder through machines. 12 Pharmacy Orientation  Surface characteristics Surface characteristics (e.g. Hygroscopicity) Hygroscopicity is the tendency of a solid to take up water from the atmosphere. Classified based on the amount or rate of water uptake when a solid is exposed to controlled relative humidity (RH) value at a specified temperature. 13 Pharmacy Orientation  Solubility analysis  Aqueous solubility  Drug pKa / Ionization at physiological pH  Partition co-efficient 14 Pharmacy Orientation  Aqueous solubility Important goal of the preformulation effort is to devise a method for making solutions of the drug. Orally administered drug must dissolve in the aqueous fluid of the gastrointestinal tract (GIT) prior to absorption. Solubility can be improved by addition of cosolvents. 15 Pharmacy Orientation  Drug pKa / Ionization at physiological pH pKa is the dissociation constant of a drug. The nonionized 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. 16 Pharmacy Orientation  Partition co-efficient Partition co-efficient influence permeation of a drug across biological membrane. Partition co-efficient is a ratio of equilibrium concentration of drug in oil phase to equilibrium concentration of drug in aqueous phase. K = C0/Cw where, C0  organic phase concentration Cw  aqueous phase concentration 17 Pharmacy Orientation  Partition co-efficient 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 excessive aqueous solubility (i.e. low oil/water partition co-efficient)  can't penetrate the membrane. 18 Pharmacy Orientation  Dissolution To know the gastrointestinal absorption and other physicochemical properties. The intrinsic dissolution rate is determined by the rotating disc method. The dissolution rate is described by Noyes- Whiteny equation. 19 Pharmacy Orientation  Stability analysis Drug stability Compatibility 20 Pharmacy Orientation  Drug stability This study includes both solutions and solid-state experiments under various conditions for handling, formulation, storage, and in vivo administration. 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,....etc. 21 Pharmacy Orientation  Compatibility Compatibility tests play a very important role in the preformulation studies of oral dosage forms. Problems arise because of the interaction with other drug substances and with 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. 22 Pharmacy Orientation ………………….. is the ability of the compound to crystallize as more than one distinct crystalline species with different internal structure. A Polymorphism B Crystal growth C Nucleation D Hygroscopicity 23 Pharmacy Orientation  It is important for the formulator of a new drug substance to know with which excipients he can work and which he can't through studying …………… tests. A solubility analysis B dissolution rate C drug stability D compatibility 24 Pharmacy Orientation Drugs with extremely high partition co-efficient readily penetrate biological membranes. √ True False Non-ionized drugs are lipid insoluble, and are transported by passive diffusion through biological membranes. True False√  27 Pharmacy Orientation