1. ERT430 Introduction (1) Course code : ERT 430 (2) Course title : Pharmaceutical Process Engineering (3) Number of unit : 3 (4) Course type : Elective (5) Prerequisite : Nil (6) Course synopsis : The course includes the principles of drug pharmacokinetics: absorption, distribution, metabolism and excretion of drugs. This course also covers the scientific and technological aspects of the designing and manufacturing of pharmaceutical products. (7) ) Learning Outcomes: At the end of the course, students are expected to be: 1.Able to explain the basic concept of drug absorption and disposition and analyze the related pharmacokinetics. 2.Able to evaluate the pharmaceutical engineering processes in pharmaceutical formulation and production. 3.Able to design pharmaceutical facilities. (8) List of possible experiments: Nil (9) Learning approach : Lecture : 100% (42 hours) (10) Evaluation contribution: (i)Examination: 70%  Midterm Examinations = 20%  Final Examination = 50% (ii) Continual Assessment: 30%  Assignments = 20%  Quizzes = 10%

2. ERT430 Introduction (11) Lecturers i.Prof Dr Awang Soh @ Yusoff Bin Mamat ii.Mrs Anis Atikah binti Ahmad iii.Mrs Syazwani binti Mahmad Puzi (12) List of text books and references Textbook: i)Bennet, B. and Cole, G. Pharmaceutical Production: An Engineering Guide. Warwickshire: Institution of Chemical Engineers (IChemE)., 2003. Reference Books: i)Aulton M. E., Pharmaceutics. The science of dosage form design. 2 nd Edition. London: Churchill Livingstone., 2002. ii)David J. am Ende, Chemical Engineering in the Pharmaceutical Industry: R&D to Manufacturing, New Jersey, USA: John Wiley & Sons, Inc., 2011. iii)Blacker A. John, Williams Mike T., Pharmaceutical Process Development - Current Chemical and Engineering Challenges, Royal Society of Chemistry, UK: Cambridge., 2011. iv)Anthony J. Hickey, David Ganderton. Pharmaceutical Process Engineering: 2 nd Edition. New York: Informa Healthcare., 2009 v)Sambamurthy K., Pharmaceutical Engineering. New Delhi: New Age International Publishers. 2012

3. ERT430 Lesson Plan WeekCourse Contents (Guidelines) Lecturer Week 1 (15 Feb - 19 Feb) INTRODUCTION TO PHARMACEUTICAL PROCESS Compare the traditional and modern way of drug usage and production. Discuss several routes for synthetic drug formation. Distinguish different flow processes /stages of new product launch. (3 hours) Mrs Anis Atikah Week 2-3 (22 Feb - 4 Mac) PHARMACEUTICS AND PHARMACOKINETICS Discuss the physiological issues involved in drug therapy; Analyze the pharmacokinetic models such as adsorption, distribution, metabolism and elimination kinetics; Analyze bioavailability, clearance and repetitive dosing; Demonstrate membrane transport of orally delivered drugs. Discuss factor influencing drug adsorption and availability. Discuss and demonstrate route of delivery on drug action; Calculate chemical kinetics and drug stability. (6 hours) Mrs Anis Atikah Week 4-5 (7 Mac - 18 Mac) PHARMACEUTICAL PARENTERAL FORMULATION: SOLUTIONS, SUSPENSIONS and EMULSIONS Discuss and define parenteral formulated products; Formulate and evaluate solutions, suspensions and emulsions; Discuss and demonstrate production eye drops, eye lotions and eye ointments; Discuss and design production facilities; Formulate and evaluate ophthalmic products. (6 hours) Mrs Anis Atikah

4. ERT430 Lesson Plan – cont. Week 6-7 (21 Mac - 1 April) PHARMACEUTICAL SOLID DOSE FORMULATION: TABLETS and CAPSULES Illustrate, formulate and evaluate of different types of solid dose formulation; Discuss, analyze and evaluate methods of preparation, processing problems, formulation and manufacturing techniques of different compressed tablets and capsules. (6 hours) Prof Dr Awang Soh Week 8 (4 April – 8 April) PHARMACEUTICAL SOLID DOSE FORMULATION: POWDERS and GRANULES Discuss, demonstrate and analyze methods of preparation, processing problems, formulation and manufacturing techniques of powders and granules. (3 hours) Prof Dr Awang Soh Week 9 (11 Apr - 15 Apr) CUTI PERTENGAHAN SEMESTER/ MID-TERM BREAK Week 10-11 (18 Apr - 29 Apr) PHARMACEUTICAL PROCESSING Describe, discuss and illustrate general technique used for extraction and isolation of phytopharmaceuticals; illustrate principles and design pilot plant for Isolation of active pharmaceuticals. (6 hours) Prof Dr Awang Soh

5. ERT430 Lesson Plan – cont. Week 12-13 (2 May - 13 May) PHARMACEUTICAL FACILITIES Discuss, illustrate and design utilities and services for the pharmaceutical (laboratory and plant) facility. (6 hours) Mrs Syazwani Week 14-15 (16 May- 27 May) PILOT MANUFACTURING FACILITIES Design pilot manufacturing facilities for the development and manufacture of pharmaceutical products. Discuss regulatory, design and operating conditions for primary and secondary production. Design of facilities and equipment. (6 hours) Mrs Syazwani Week 16 30 May-3 June) REVISION WEEK Week 17-19 6 June -26 June) FINAL EXAMINATION

6. PHARMACEUTICAL PROCESS ENGINEERING CHAPTER 1 – INTRODUCTION MRS ANIS ATIKAH AHMAD anisatikah@unimap.edu.my

7. DEFINITION OF DRUG Substances intended for use in the diagnosis, cure, mitigation or prevention of disease in man or animals; substances (other than food) intended to affect the structure or any function of the body of man or animals; substances intended for use as a component of any substances specified above but does not include devices or their components, parts or accessories

8. TRADITIONAL VS MODERN WAY OF DRUG USAGE & PRODUCTION 1. TRADITIONAL WAY: Trial & error : by looking at the effect of consumption Discovered that small quantities of drugs are useful and larger quantities intake are not necessarily better (usually harmful) Direct consumption of medication: alcohol, coca leaves, poppy juice

9. TRADITIONAL VS MODERN WAY OF DRUG USAGE & PRODUCTION MODERN WAY: Needs to follow a path or process before can be sold Once an active product has been discovered and proven to be medically effective, the manufacturer has to produce the active ingredient and process it into the most suitable dosage form Very costly: can cost up to 300 million USD/drug (involves R&D, manufacturing, distribution, marketing & sales.)

10. SYNTHETIC DRUG FORMATION Synthetic route for 6a methylprednisolone (steroid) Synthetic route for phenylbutazone

11. STAGES IN NEW PRODUCT LAUNCH Discovery of active substance Pre-clinical trials Clinical trials Registration & Launch Approx 8-10,000 potential candidate substances screened for therapeutic activity Synthesis of active substance Screened for pharmacological activity Toxicity trials Pharmacokinetic trials Phase 1 Phase 2 Phase 3 Registration with health authorities Launch & sales 0.5 yr 2/3 yr Approx 1 yr Approx 2 yr 2/3 yr Development of formulations Bioavailability of formulations Stability tests on drugs & formulations Quality control methods devised Process development Detailed animal pharmacology Synthesis of radio labelled material Blood level methods developed Acute & 6 month toxicity studies Reproduction studies & teratology Absorption, excretion, & metabolism on animal species Outline clinical trial programmes Development of formulations Bioavailability of formulations Stability tests on drugs & formulations Quality control methods devised Process development Detailed animal pharmacology Synthesis of radio labelled material Blood level methods developed Acute & 6 month toxicity studies Reproduction studies & teratology Absorption, excretion, & metabolism on animal species Outline clinical trial programmes Establishment of manufacturing processes Plant design & buildings Development of sales formulation Bioavailability studies Package development Stability studies International clinical trials Detailed absorption, excretion & metabolism studies in man Establishment of manufacturing processes Plant design & buildings Development of sales formulation Bioavailability studies Package development Stability studies International clinical trials Detailed absorption, excretion & metabolism studies in man Activity & pre-clinical safety 2-4yrs The time cycle from discovery to launch takes many years and will probably not be less than four years for a New Chemical Entity (NCE).

12. Common terms Primary Production: manufacture of the active ingredient Secondary Production: turning the active ingredient into the dosage forms

13. Dosage forms available for different administration routes Administration routesDosage forms OralSolution, syrup, suspension, emulsion, gel, powders, granules, capsules, tablets RectalSuppositories, oitments, creams, powders, solutions TopicalOintments, creams, paste, lotions, gel, solutions, topical aerosols ParenteralInjection (solution, suspension, emulsion forms), implants, irrigation and dialysis solutions RespiratoryAerosols (solution, suspension, emulsion, powder forms), inhalations, sprays, gases NasalSolutions, inhalations EyeSolutions, creams, ointments EarSolutions, suspension, creams, ointments

14. Common terms Pharmacokinetics: The study and characterization of the time course of drug absorption, distribution, metabolism and elimination(ADME) Bioavailability: The relative amount of an administered dose of a particular drug that reaches the systemic circulation intact and the rate at which this occurs (the rate and extent of drug absorption).