Introduction

Mohammad Mahareeq

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

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.

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

Introduction

• Materials + machines (equipment) Product Men (personnel) Large – scale prod. Methods (procedures) Consistent Management Approved quantity Documentation• Product constituents:i. Active pharm. Substanceii. Intermediatesiii. Excipients

Introduction• Raw materials: APIs Inactive materials1. APIs Produced through certain chemical processes: Nitration Sulfonation Halogenation Friedel-crafts Acylation Esterification Hydrolysis Amination Diazo Oxidation Reduction Photochemistry

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

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

Introduction

Purpose• pH control• Preservative• Antioxidant• Solvent• Surfactant• Ointment base• Flavour

ExampleCitric acid, NaCO3

Na Benzoate, PhenolAscorbic acid, Na BisulfiteAlcohol, WaterCetyl alcoholPetrolatum, PEGPeppermint oil, Menthol

2. Excipients: non active materials added to formulations for different purposes:

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

Routes of administrationRoute Dosage form

oral Tab., caps., solutions, susp., powders, emulsions, gels, lozenges

Topical Oint., cream, pastes, lotions, gels, solutions

Parenteral Injections (iv, sc, im, ip, it (intrathecal), ia (intraarterial)…..

Transdermal Oint., creams, lotions, patches, infusion pumps

Intraocular/nasal/aurel Solutions, suspensions

Pulmonary aerosols

Rectal Solutions, oint., suppositories

Vaginal Solutions, oint., supp., gels, foams

Urethral Solutions, supp.

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

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

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 ApplicationANDA = Abbreviated New Drug Application

NCE – Phases of Product Development

Preclinical Testing

Phase I Phase II Phase III FDA Review

Phase IV

Years 3.5 1 2 3 2.5

Test population

Laboratory & animal studies

20-80 healthy volunteers

100-300 patient volunteers

1000-3000 patient volunteers

Review process/ Approval

Additional Post marketing 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

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 containerProduction equipmentCountry in which to market the drug