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8/11/2019 0-Admin & Introduction

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Module: CH4106: Formulation of active pharmaceutical

ingredients (API) dosage forms

Contacts: Zaher Judeh

Tel: 6790-6738

[email protected]

N1.2 B1-14

Textbook: H.C. Ansel, L.V. Allen Jr., N.G. Popovich,

Pharmaceutical dosage forms and drug

delivery systems, 8th Edition, Lippincott

Williams & Wilkins

Welcome to Formulation


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Teams: Preselected 12 teams each of 8 students

with a team leader and a deputy team leader Readiness assurance

Reading outside class time: PowerPoint slides, lecture

videos and other reading materials will be uploaded on

edventure

Individual assessment (during class, 30-35 min.)

Team assessment (during class, 30-35 min.)

Application activities Presentation on a selected topic

Case studies discussion

Team-Based Learning


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Application activities How?

A problem will be given during class time Teams will be given 20 minutes to discuss the problem

and arrive at a solution. Teams are allowed to refer to any

material/resource to answer the problem.

Solutions (1 written page) will be collected from all teams

Only 6 teams will be selected randomly to present their

solutions each class (10 minutes only).

Presenting teams will be marked by all teams (11 teams) Peer assessment: within the team (in week 12). This will

also include a statement on:

One thing they appreciate from the member

One thing they request from the member

Team-Based Learning Cont.


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Assessments/Examinations

May include multiple choice, true/false, short/long answer,

essay questions, and problems anything! Exams can be on any selected topic:

In class individual assessment up to 12%

In class team assessment I up to 10% In class team assessment II up to 13%

Peer assessment (in week 12) up to 10%

CA Monday 20/10/2014 9:35-10:35 am up to 10% Final exam University sets date up to 45%

Students are expected to take examinations at the

scheduled time.


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CA/Assessment Policy

If student misses CA due to following valid reasons:

Valid MC (not from Chinese doctor) Passing away of immediate family (parents, siblings,

grandparents)

Participate in an activity representing NTU There will be no makeup CA.

The best 8 assessments will be computed towards your

final mark. Students who are absent from lectures without

valid reason will get (0) zero for that assessment.

Marks will be computed according to NTU prevailing

policy.


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The slides represent points for discussion

You must refer to the textbook for a complete account

If it is mentioned, it is required, otherwise it is for yourreading pleasure!

Have Fun and Good Luck

Attention


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Course Contents

Section I: Introduction to Drugs, Drug Dosage Forms

and Drug Delivery Systems Introduction to Drugs and Pharmacy

New Drug Development and Approval Process

Current Good Manufacturing Practices Section II: Drug Dosage Form and Drug Delivery

System Design

Dosage Form Design: Pharmaceutics and

Formulation Considerations

Dosage Form Design: Biopharmaceutic and

Pharmacokinetic Considerations


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Course Contents Cont.

Section III: Solid Dosage Forms and Solid Modified-

Release Drug Delivery Systems Powders and Granules

Capsules

Tablets Solid Oral Modified-Release Dosage Forms and Drug

Delivery Systems

Section IV: Semi-Solid Dosage Forms and Transdermal

Systems

Ointments, Creams and Gels

Transdermal Drug Delivery Systems


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Course Contents Cont.

Section V: Pharmaceutical Inserts

Suppositories and Inserts Section VI: Liquid Dosage Forms

Solutions

Disperse Systems Section VII: Sterile Dosage Forms and Delivery

Systems

Parenterals

Ophthalmic Solutions and Suspensions


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Overall Goals

For a given drug, understand how to select an

appropriate drug delivery system, formulation, route ofadministration based upon the chemical, physical and

biological attributes of the drug

Inspire YOU: This is a great field where more researchand development for optimum dosage form design is to

be done!


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Course Objectives: Understand

The process of drug development and approval

The pre-formulation considerations applicable to thedesign of specific dosage forms

The biological and physicochemical properties of drugs

that must be considered in the design of pharmaceutical

dosage forms

The concepts of chemical kinetics, drug stability and the

factors that impact dosage forms stability

Different dosage forms and outline their advantages andshortcomings


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Course Objectives Cont. Be familiar with common dosage forms in use today and

current development in drug delivery systems -- Research

Understand formulation of a dosage form with respect to:

Types and functions of the additives/excipients used

Problems encountered during the formulation of a

specific dosage form Techniques used in the production of different dosage

forms


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What is Pharmaceutics?

The science of dosage form design where the API is

made into a safe and effective medication It applies science and engineering knowledge to the

multidimensional problems of the formulation,

development, evaluation, production, distribution,

selection and administration of safe, effective, reliable,

drug delivery systems

Pharmaceutics include:

Pharmacokinetics, Pharmacodynamics,Pharmacogenomics, Pharmaceutical formulation,

Pharmaceutical technology


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Preformulation: characterization of a drug's physical,

chemical, and mechanical properties in order to choosewhat other ingredients should be used in the preparation

Formulation: the process in which the API (drug) and

excipients are combined to produce a final medicinal

product

TheAPI must be delivered to the patient in some way

Dosage Form

Preformulation / Pharmaceutical

Formulation


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Dosage Form

The physical form in which a drug is produced for

administration by the appropriate route to the recipient It functions as a drug delivery system (DDS) get the

drug to its site of action

The design and formulation of a dosage form affects therate and amount of drug delivered bioavailability

When designing a dosage form we must consider:

Rate of delivery

Site of release

Target delivery to specific cells/receptors (action)


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Current R&D Scenario:Pharmaceutical industry

Activities broadly divided into

Search for novel molecules/treatment modalities Development of novel drug delivery systems ( or novel

dosage forms)

Situation very similar to arms / weapons industry:

New and more powerful bombs

Programmable & smarter rockets/delivery systems

Mutually complementary:

To be effective a bomb must hit the correct target Many obstacles to reach the target

Delivery system suppose to overcome obstacles

A good rocket with no potent warhead is ineffective


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Likewise in Drug Therapy! Optimal drug response depends upon:

Using the correct drug Delivery in most appropriate manner

Reach intended site only

Leave other tissues / organs alone

Sufficient quantity

Suitable duration

Problems to fulfill these requirements best exemplified in

cancer chemotherapy


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Race Between Bomb and Rocket Development of novel molecules is the winner

Progress made in delivery systems lacking behind Situation made worse by biotech revolution:

biotherapeutics

Cannot be delivered by conventional delivery

systems E.g.: gene therapy


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Design Criteria for Dosage Form

Must be safe, effective and on target

Must be stable and has a reasonable shelf-life Components must not react with the storage container

Tolerate physiological variables in stomach and liver

Must have patient acceptability: color, taste, smell,appearance, size

Must permit efficient, cost-effective production that

provides accuracy and precision of dosing


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Drug Delivery: Challenges

Attaining accuracy and precision of low dose drugs

A drug (dose = 0.1 mg) formulated into a typical 200mg tablet has a drug/excipient ratio of 1:2000

Stabilization and delivery of large molecules (peptides

and proteins)

Overcoming the practical problem where large dose

drugs lack the properties to be formed directly into tablets

Delivery of poorly soluble and/or poorly permeable drugs

Design of customize drug delivery: provide non-constantdrug release rates; pulsed, ramped or once-a-day (24

hour) delivery


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Various Systems for Nitroglycerine

Dosage

Form

Dosage

(mg)

Onset of

action(min.)

Peak

action(min)

Duration of

action(min/h)

Sublingual 0.3-0.8 2-5 4-8 10-30 min

Buccal 1-3 2-5 4-10 30-300 min

Oral 6.5-19.5 20-45 45-120 2-6 h

Patches 5-10 30-60 60-180 Up to 24 h

Ointment 0.5-10inc 15-60 30-120 3-8 h

https://rxsecure.umaryland.edu/courses


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Drug Delivery Systems/Dosage

Forms Classifications Classification:

Local/topical or systemic therapy Immediate/conventional or Modified/novel release

Local/topical therapy

Therapeutic agent applied directly to site of action

IV

Oral Systemic therapy

Drug administered systemicallyinto blood to be transported to

site of action


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Systemic: Oral therapy can

result in severe toxic effectsLocalized therapy using meter

dose inhaler. Toxic effects can

be avoided if used properly


Forms


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Forms Classifications Conventional/immediate release preparations:

Job is done after delivering drug to site ofabsorption/action

E.g.: normal tablets, capsules, creams, ointments,

injections

Novel/modified release system:

Additional functions, e.g.: control rate of absorption,

promote absorption, site targeting, ultimate is tofunction like a guided missile - essentially to maximize

therapeutic response and minimizing side effects

(discussed in more detail later)


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Modified Release Dosage Forms

Dosage forms whose drug-release characteristics of time-

course and/or location are modified: Delayed release

Extended (sustained) release

Delayed Release:

Release of a drug (or drugs) at a time other thanimmediately following oral administration, e.g.

Enteric coated: Prevents release of drug in stomach;releases after passing phyloric sphincter

Pulsatile delivery: programmable to release drug atpredetermined time or place


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Modified Release Dosage Forms

Extended (sustained) release

Any product formulated to make the containedmedicament available over an extended period of time

after ingestion

Provide a reduction in dosing frequency as compared

to the same drug presented in a conventional

immediate release dosage form

Controlled release

Prolonged release


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Mechanism of Drug Absorption Paracellular:

Through gaps/pores between cells Small molecules e.g. urea, water

Transcellular: Through cells hence biological membranes

Main mechanism, diffusion: follows Ficks law

molecules must have lipid solubility, unionised form Active transport: energy involved, against conc

gradient carrier can be saturated, eg vit B1, B2, B3 B6

Facilitated diffusion: carrier can be saturated, noenergy involved, not against conc gradient, eg B12

Pinocytosis, endocytosis molecules (large) like somepeptides, particles


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If absorption is rate limiting, bioavailability no longer governedby physicochemical properties and formulation variables

http://www.boomer.org/c/p1/Ch03/Ch0302.html

Drug-plasmaprotein complex

Adiposetissue

storage

Effector tissues,drug receptor

bindingLung

Peripheraltissue,

Metabolism

KidneyLiver,

drugmetabolism

Bile

DrugDrug

Blood

Intestines

Oralingestion

Volatile drugsin expired air

Drugs &metabolites in

urine

Drugs &metabolites in

stool

Intestinalreabsorption

Drug Action


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From the equation: dissolution is affected by

physicochemical properties and formulation variables

C)(CshV

DA

dt

dC

layediffusionofthicknessh

tcoefficiendiffussionD

areasurfaceAratendissolutiodt

dC

mediuofvolumeV

solubilityCs

mediuinionconcentratC

Noyes-Whitney Equation

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