Lecture 1.pptx

Advanced drug delivery systems Lecture 1 Presented by: Dr. Amira Boseila sinaiuniversity.net  ‫الرؤية‪:‬‬ ‫كلي ة الص يدلة جامع ة س يناء فرع القنطرة كلي ة معتمدة تحق ق جمي ع معايي ر‬...

Advanced drug delivery systems Lecture 1 Presented by: Dr. Amira Boseila sinaiuniversity.net  ‫الرؤية‪:‬‬ ‫كلي ة الص يدلة جامع ة س يناء فرع القنطرة كلي ة معتمدة تحق ق جمي ع معايي ر‬ ‫الجودة في التعليم والبحث العلمي وخدمة المجتمع‬ ‫الرسالة‪:‬‬ ‫تلتزم كلي ة الص يدلة ‪ -‬فرع القنطرة جامع ة س يناء بإعداد ص يدلي متمي ز ف ي‬ ‫مجاالت س وق العم ل وتطوي ر الص ناعة الص يدالنية عل ى المس تويين المحل ي‬ ‫واإلقليم ي وإعداد باح ث علم ي متمي ز يس اهم بشك ل فعال ف ي تنمي ة البيئ ة‬ ‫وتعظي م االس تفادة م ن موارده ا لخدم ة المجتم ع م ن أج ل تحقي ق متطلبات‬ ‫الجودة الشامل ة والحفاظ عل ى القي م واألخالقيات المهني ة وتقالي د المجتم ع‬ ‫ومواكبة العلم والتكنولوجيا الجديدة‪.‬‬ “Preformulation studies” Lecture 1 sinaiuniversity.net Lecture objectives Identification of physicochemical properties of drug molecules. What is the difference between crystallinity, amorphism, and polymorphism? How to characterize fine powders?  Introduction Before the development of a formulation or dosage form, it is essential that certain properties of a drug molecule are to be determined. This information decides many of the subsequent events and approaches in formulation development Preformulation – phase of research and development in which the physical and chemical properties of a drug molecule are studied to develop a safe, effective, and stable dosage form. Preformulation commences when a newly synthesized drug shows sufficient pharmacological promise in animal models to warrant evaluation in man. First step in rational development of a dosage form of a drug substance. Physico-chemical characterization A) Physical properties of drug substances  Organoleptic characterization  Bulk characterization  Solubility profile B) Chemical properties of drug substances  Hydrolysis  Oxidation  Reduction  Racemization  Polymerization  A) Physical properties of drug substances The physical properties of drug molecules can affect the I) Organoleptic structure and stability of characterization formulations and may also alter the bioavailability of the Refers to evaluation of drugs from the dosage forms. drug on the basis of Hence, the physical properties color, odor, texture, and of drugs are important in the taste. dosage form design. There are three categories of physical properties that influence dosage form design A) Physical properties of drug substances II) Bulk characterization Bulk characterization Bulk characterization of drug molecules involves the includes; characterization of various solid– state properties that could change during the process  Crystallinity, amorphism, development. and polymorphism  Density of drug Variability of bulk substances characterizations, significantly proves subsequent events and  Powder flow properties approaches in the drug development process.  1. Crystallinity Crystal compounds are characterized Crystallinity has a by repetitious spacing of constituent atoms or molecules. greater effect on the Crystals can be of different shapes. absorption of drugs. E.g. cubic, tetragonal, orthorhombic, etc The crystal habit and crystal internal structure of a drug can affect the bulk and flow properties as well as chemical stability. Crystal habit – the outer appearance of a crystal Internal structure – molecular arrangement within the solid Degree of crystallinity affects the hardness, density, transparency, and diffusion.  2. Amorphism Amorphous compounds are those whose atoms or molecules are randomly placed. Internal structure shows a major distinction whether the solid is crystalline or amorphous. Some drugs can exist in an amorphous state. They are typically prepared by rapid precipitation and lyophilization. Such drugs represent the highest energy state, or higher thermodynamic energy than the crystalline form. The amorphous form is less stable than the crystalline form. The solubility of the amorphous form is greater than its crystalline state. Upon storage, amorphous solids tend to revert to more  3. Polymorphism When a substance exists in more than one crystalline form. Polymorphs are of two types; a) Enantiotropic polymorphs: refers to the state of having different polymorphic states that are stable at different temperatures. (e.g. sulphur) b) Monotropic polymorphs: refers to the state of having only one polymorph that is stable at all the reasonable temperatures. (e.g. glyceryl stearate) Polymorphs differ from each other concerning their physical properties like solubility, melting point, density, etc. Depending on the stability: one form will be more stable than the other. Such stable forms have a lower energy state, high melting point, and least aqueous stability. Other forms are called metastable forms with the opposite properties. Determined by differential scanning calorimetry, and x-ray diffraction methods. Fine particle characterization Bulk flow, formulation homogeneity and surface controlled processes such as dissolution and chemical reactivity are directly affected by size, shape, and surface morphology of drug particles. 1. Particle size Size affects: drug release from dosage forms, drug absorption, therapeutic action, physical stability of dosage forms like suspension and emulsions, flow properties of powders like interference in the flowability of the powder Particle size generally denoted in micrometers How to measure the particle size? 1) Optical microscopy 2) Sedimentation method 3) Light scattering method 4) sieving Fine particle characterization 2. Particle shape 3. Particle surface area Shape influences the surface area, flow properties, packing, and Size and surface area are compaction of the inversely proportional to particles. each other Spherical particles have The smaller the drug minimum surface area particle, the greater the and better flow properties. surface area. Shape also influences the Maximum surface area rate of dissolution of ensures better solubility. drugs. Flow properties of materials  Flow properties can be affected by a number of  In the case of powders factors like: changes in flow properties are particle size, shape, surface measured by; area, density, frictional forces, van der waal forces etc. 1) Hausner’s ratio  Efficient flow of particles is 2) Carr’s compressibility needed for an effective complex formulation. 3) Angel of repose  In case of liquid materials flow properties are measured using rheology. What is the effect of each of the following on flow properties? 1) Moisture content: reduces the flow properties of the particles 2) Nature of particles: round and smooth surface particles show good flow properties. 3) Particle size: smaller particle size gives better flow properties