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: i.Diagnosis, treatment, mitigation or prevention of a disease, a disorder, an abnormal physical state or the symptoms thereof in humans or animals ii.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: i.Active pharm. Substance ii.Intermediates iii.Excipients

6. Introduction Raw materials: APIs Inactive materials 1.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 Purpose pH control Preservative Antioxidant Solvent Surfactant Ointment base Flavour Example Citric acid, NaCO 3 Na Benzoate, Phenol Ascorbic acid, Na Bisulfite Alcohol, Water Cetyl alcohol Petrolatum, PEG Peppermint oil, Menthol 2. Excipients: non active materials added to formulations for different purposes:

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 RouteDosage form oralTab., caps., solutions, susp., powders, emulsions, gels, lozenges TopicalOint., cream, pastes, lotions, gels, solutions ParenteralInjections (iv, sc, im, ip, it (intrathecal), ia (intraarterial)….. TransdermalOint., creams, lotions, patches, infusion pumps Intraocular/nasal/aurelSolutions, suspensions Pulmonaryaerosols RectalSolutions, oint., suppositories VaginalSolutions, oint., supp., gels, foams UrethralSolutions, supp.

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 Preclinical Testing Phase IPhase IIPhase IIIFDA Review Phase IV Years 3.5123 2.5 Test population Laboratory & animal studies 20-80 healthy volunteers 100-300 patient volunteers 1000-3000 patient volunteers Review process/ Approval Addition al Post marketin g testing Purpose Assess safety & biological activity Determine safety and dosage Evaluate effectiveness, look for side effects * Verify effectiveness, monitor adverse reactions from long-term use Success rate 5000 compounds evaluated 5 enter trials 1 approved *: 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 processes and 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