Lec 10: Pharmaceutical

Raw Materials → Chemical/Biological Processing → Active Pharmaceutical Ingredient (API) → Drug Formulation → Finished Drug Product → Packaging and Distribution

The basic industrial transformation in the pharma industry

Innovative Pharmaceutical Companies

Companies that discover and develop new medicines

Generic Pharmaceutical Industry

Produces equivalent medicines after patent expiration

Biotechnology Pharmaceutical Industry

Uses biological systems to manufacture vaccines, proteins, antibodies, hormones

Contract Manufacturing Organizations

Companies that manufacture pharmaceutical products for other companies

Herbal medicines → isolation of active compounds → synthetic drugs → antibiotic production → biotechnology growth → advanced drug delivery

Development of Modern Pharmaceutical Industry

Pharmacopoeia standards

This major regulatory requirement defines drug quality specifications

Drug Substance or Active Pharmaceutical Ingredient

the chemically or biologically active component responsible for therapeutic action

Drug Product

contains API + excipients + dosage form

Drug Discovery → Lead Compound Identification → Laboratory Testing → Clinical Trials → API manufacturing → Formulation Development → Commercial Production

Drug Development Process

Tablets

compressed solid dosage form

Capsules

drug enclosed in gelatin shell

Syrups

liquid preparation

Suspensions

solid particles dispersed in liquid

Creams

semi-solid topical products

Injections

sterile liquid preparations

Inhalers

drug delivered through respiratory system

Selection of API → Addition of excipients → Mixing/Blending → Granulation → Compression or filling → Coating → Testing

What are the general formulation steps in the pharmaceutical formulation process?

Active Pharmaceutical Ingredient

the biologically active component of a pharmaceutical product that produces the intended therapeutic effect

• Chemical synthesis (paracetamol, aspirin)

• Fermentation-based production (penicillin, antibiotics)

• Biotechnology production (insulin, monoclonal antibodies)

What are the three types of API manufacturing

Raw Mats → Material Preparation → Chemical/Biological Reaction → Reaction Completion → Isolation of Product → Purification → Crystallization → Solid-liquid Separation → Drying → Milling/Sieving → API testing → Finished API

General industrial pathway of API manufacturing

Organic chemicals

The raw material for API production that serves as starting molecules for synthesis

Inorganic chemicals

The raw material for API production that serves as the catalysts and reagents

Biological materials

The raw material for API production that is used in fermentation

Solvents

The raw material for API production that is used for reaction and purification

Catalysts

The raw material for API production that improves reaction efficiency

Chemical Synthesis of APIs

It involves converting simple chemical molecules into complex pharmaceutical compounds through controlled chemical reactions

Starting Materials → Chemical Reaction → Intermediate Formation → Further reactions → Final API Formation → Purification

General chemical synthesis sequence

Salicylic Acid + Acetic Anhydride → Acetylsalicylic Acid (Aspirin) [esterification]

What is the manufacturing reaction of aspirin?

Oxidation

functional group modification

Alkylation

carbon-carbon bond formation

Hydrolysis

bond cleavage

Condensation

molecular combination

Fermentation-based API Manufacturing

Some pharma products cannot be economically produced through chemical synthesis. instead, microorganisms are used as biological factories. (ex: antibiotics, vitamins, enzymes, amino acids)

Microorganism selection → Culture preparation → Fermentation reactor → Product recovery → Purification → API

Fermentation Process Flow

Temperature

Which parameter is important for microbial growth control

pH

Which parameter is important for maintaining biological activity

Oxygen supply

Which parameter is required for aerobic organisms

Nutrient concentration

Which parameter is important for controlling productivity

Penicillium Mold → Fermentation tank → Broth Recovery → Extraction → Purification → Penicllin API

Penicillin Production Process Flow

Biotechnology-based API Production

Modern pharmaceutical industries increasingly use biotechnology (ex: insulin, growth hormones, vaccines, antibody therapies)

Genetic engineering → Cell line development → Cell culture → Bioreactor operation → Product recovery → Purification → Biological API

Biotechnology Production Flow

Chromatography

major purification operation that is based on selective adsorption and is used for high-purity separation

Crystallization

major purification operation that is based on phase equilibrium and is used to obtain pure crystals, it is also one of the most important pharma separation process

Dissolved API Solution → Cooling/Solvent Removal → Crystal Formation → Filtration → Drying

Crystallization process

Solid-Liquid Separation

After crystallization, API crystals must be separated from liquid (filter press, centrifuge, vacuum filter)

Vacuum dryer

this type of dryer is used for heat-sensitive APIs

Particle Engineering and Milling

After drying, APIs may require size adjustment (mill, sieve, blender)

API + Pharmaceutical Excipients → Formulation Development → Dosage Manufacturing → Finished Drug Product → Packaging and Distribution

Drug Product Manufacturing Process

Excipients

these are inactive ingredients added to improve manufacturing, stability, and performance

Diluent

increases bulk volume (ex: lactose)

Binder

holds tablet ingredients together (ex: starch)

Disintegrant

helps tablet break apart (ex: cellulose)

Lubricant

reduces friction during compression (ex: magnesium stearate)

Preservative

prevents microbial growth (ex: parabens)

Stabilizer

maintains chemical stability (ex: antioxidants)

Coating agent

protects tablet surface (ex: polymers)

dosage form

this determines how the drug is delivered into the body

Tablets

this dosage form represents one of the most common pharmaceutical products

Raw materials → Dispensing → Mixing/Blending → Granulation → Drying → Milling → Lubrication → Compression → Coating → Inspection → Packaging

Tablet Manufacturing Process Flow

Dispensing

dispensing the correct quantities of APIs and excipients which are measured according to formulation requirements

Mixing and Blending

done to achieve uniform distribution of API throughout the formulation

Granulation

process done to convert fine powders into larger particles called granules, this improves flowability, compression, and prevents segregation

• Wet granulation

• Dry granulation

• Direct compression

Types of Granulation

Drying | fluidized bed dryer

removes moisture after granulation | equipment used in rapid drying

Tablet Compression

after drying, this process converts granules into tablets

Compression pressure

This factor in compression process determines tablet strength

Particle size

This factor in compression strength affects flow behavior

Moisture content

This factor in compression affects stability

Uniformity

This factor in compression ensures accurate dosage

Coating

This part of the tablet manufacturing process provides protection, improved appearance, masks taste, and controls drug release

Enteric coating

prevents stomach dissolution

API + Excipients → Blending → Capsule Filling → Closing → Inspection → Packaging

Capsule Manufacturing Process

Water Preparation → Ingredient Dispensing → Mixing → Heating/Cooling → Filtration → Filling → Packaging

General Process Flow of Liquid Pharmaceutical Manufacturing

• Clean rooms

• Sterile equipment

• Controlled air quality

• Aseptic processing

Sterile Manufacturing Requirements

• Critical area - direct product exposure

• Supporting area - preparation activities

• Controlled area - material handling

Cleanroom classifications

Packaging

an essential pharmaceutical operation because it protects the product from moisture, oxygen, light, contamination, and physical damage

• Protection

• Preservation

• Identification

• Safety

• Convenience

Functions of pharmaceutical packaging

Primary packaging

This packaging directly contacts the medicine (glass vials, plastic bottles, aluminum blisters, gelatin shell)

Secondary packaging

This packaging provides additional protection (cartons, boxes, labels)

Tertiary packaging

This packaging is used for transportation (shipping containers, pallets)

Finished product → Inspection → Primary packaging → Secondary packaging → Labeling → Storage → Distribution

Packaging process flow

Identity test

QC testing that confirms correct drug

Assay testing

QC testing that determines API concentration

Purity testing

QC testing that detects impurities

Dissolution testing

QC testing that measures drug release

Stability testing

QC testing that determines shelf life

Microbial testing

QC testing that ensures safety

• Chromatography

• Spectroscopy

• Titration

• Physical analysis

Chemical Testing

• Sterility testing

• Endotoxin testing

• Microbial limit testing

Microbiological testing

Good Manufacturing Practice

a system that ensures pharmaceutical products are consistently produced and controlled according to quality standards (Personnel, Facilities, Materials, Equipment, Documentation, Validation, Quality Systems)

Validation

It demonstrates that a manufacturing process can consistently produce quality products. It has four types: process, equipment, cleaning, and analytical

Chemical/Biological Raw Mats → API Manufacturing → Purification and Testing → Formulation Development → Dosage form production → QC → Packaging → Distribution → Patient Use

Integrated Process View from Raw Material to Medicine

Chemical Oxygen Demand

The parameter in pharmaceutical wastewater characteristics which indicates organic pollutant concentration

Pharma Wastewater → Screening → pH adjustment → Chemical treatment → Biological treatment → Advanced treatment → Safe discharge

General Treatment Process

Activated carbon adsorption

An advanced treatment technology that removes organic compounds

Membrane filtration

An advanced treatment technology that separates contaminants

Advanced oxidation

An advanced treatment technology that breaks down persistent chemicals

Ozonation

An advanced treatment technology that oxidizes pharmaceutical residues

Atom economy

Green Chemistry Principle that maximizes material conversion