Pharmaceutical Product Development Overview

1. Introduction Mohammad Mahareeq

2. Introduction Definitions • Technology: The application of science to industrial or economical objectives • Drug: Any substance or mixture of substances manufactured, sold or represented for use in: • Diagnosis, treatment, mitigation or prevention of a disease, a disorder, an abnormal physical state or the symptoms thereof in humans or animals • Restoring, correcting or modifying organic functions in humans or animals

3. Introduction • Active pharmaceutical ingredient (API): Any substance or mixture of substances intended to be used in the manufacture of a pharmaceutical dosage form and that, when so used, becomes an active ingredient of that pharmaceutical dosage form. • Bulk product: Any product that has completed all processing stages up to, but not including, final packaging.

4. Introduction • Pharmaceutical product: Any material or product intended for human or veterinary use presented in its finished dosage form. • Finished product: A finished dosage form that has undergone all stages of manufacture, including packaging in its final container and labelling. • intermediate product: Partly processed product that must undergo further manufacturing steps before it becomes a bulk product. • Pharmaceutical Development: The road from API to a finished product in its primary packaging material, including production methods and all necessary documentation

5. Introduction • Materials + machines (equipment) Product Men (personnel) Large – scale prod. Methods (procedures) Consistent Management Approved quantity Documentation • Product constituents: • Active pharm. Substance • Intermediates • Excipients

6. Introduction • Raw materials: • APIs • Inactive materials • APIs • Produced through certain chemical processes: • Nitration • Sulfonation • Halogenation • Friedel-crafts • Acylation • Esterification • Hydrolysis • Amination • Diazo • Oxidation • Reduction • Photochemistry

7. Introduction • Using certain unit operations: • Heating/Cooling • Mixing • Drying • Crystallization • Distillation • Precipitation • Filtration • Extraction • Milling = Particle size Reduction

8. Introduction • Sources of APIs: • Natural products and Extracts (e.g. carbohydrates, glycosides, lipids, proteins, alkaloids, volatile oils, plants exudates (resins, oleoresins, gum resins, balsams), enzymes, prostaglandins, hormones, vitamins, antibiotics……etc ) • Synthetic products: Total synthesis • Semi- synthetic products: partial synthesis • Nature of APIs: • Organic • Inorganic • Names of APIs: • Chemical: Systemic name, IUPAC name, Trivial name • Generic name: nonproprietary name, USAN,…..etc

9. Introduction 2. Excipients: non active materials added to formulations for different purposes: Purpose • pH control • Preservative • Antioxidant • Solvent • Surfactant • Ointment base • Flavour Example Citric acid, NaCO3 Na Benzoate, Phenol Ascorbic acid, Na Bisulfite Alcohol, Water Cetyl alcohol Petrolatum, PEG Peppermint oil, Menthol

10. Introduction • Drug products dosage forms: • Solids: tablets, capsules, powders, granules • Liquid: solutions, syrups, elixirs, suspensions, emulsions • Semi-solids: cream, ointment, gel, emulgel, paste, suppository • Specialty: gases, aerosols, transdermal patches, inhalation sprays

11. Routes of administration

12. Introduction Needs for dosage forms: • Provide safe and accurate delivery of given dosage • Protect drug from environmental degradation • Protect drug from GI degradation • Conceal bitter, salty taste, offensive odour • Allow for administration of poorly soluble drugs • Provide rate- controlled action • Allow for administration by desired route

13. Introduction • Drugs are seldom administered alone • Given as formulation • Contain additional ingredients (i.e. excipients) • Objectives of dosage form design: To achieve a predictable therapeutic response to drug included in a formulation. • In formulation we must consider physical, chemical, and biological properties of all components

14. Drug Product Development (DPD) • Different DPD approaches are generally used to produce: • New drug products- NCE, 3 Phases, (NDA). Brand Product • Product Line Extension: New Dosage Form, New Strength • Generic drug products- "one" phase (ANDA) NCE = New Chemical Entity NDA = New Drug Application ANDA = Abbreviated New Drug Application

15. NCE – Phases of Product Development • *: Drug Formulation

16. Drug Product Development (DPD) • Activities and information required to develop drug product: • Preformulation:the investigation of all chemical and physical properties of the drug substance (API) in question, which are considered important in the formulation of a stable, effective and safe dosage forms. • Formulation: to find the balance between API, Excipients, manufacturing processesand delivery form in a highly regulated environment. • Final Drug Product: Considerations to be taken • ( colour, shape, size, taste, flavor, viscosity, skin feel, and physical appearance of the dosage form) • Size and shape of the package container • Production equipment • Country in which to market the drug