This document discusses key aspects of preformulation and formulation development. It begins with definitions of important terms like drug, dosage form, dose, and bioavailability. It then describes the basic preformulation studies conducted like solubility, pH, and stability testing. The document outlines the main components of a dosage form including active drug and excipients. It provides examples of various dosage forms like tablets, capsules, liquids, semisolids, and inhalations. Finally, it stresses the importance of following formulation development steps to create an efficient dosage form that is safe, effective and has minimal toxicity.
3. Definitions
Drug is any substance or product that is used or is intended to be used to modify
or explore physiological states for the benefit of the recipient
Dosage forms are a mixture of active drug components and nondrug
components
Dose is defined as quantity of medication that is to be administered at each time
to produce a certain degree of response in a patient
Bioavailability is defined as the rate and extent of absorption of unchanged drug
from its dosage form
4.
5. Preformulation involves the application of
biopharmaceutical principles to the physicochemical
parameters of a drug with the goal of designing an
optimum drug delivery system.
Characterization of drug molecule is a very
important step at the preformulation phase of
product development.
6. Following studies are conducted as basic preformulation studies,
special studies are conducted depending on the type of dosage form
and the type of drug molecule
Solubility determination
pH & pKa determination
Partition coefficient
Solid state properties ( polymorphism and amorphism)
Powder flow properties
Stability studies
7.
8.
Active drug substance (active pharmaceutical ingredient - API)
Excipients (inactive pharmaceutical ingredients)
◦ Technological, biopharmaceutical and/or stability reasons
◦ Diluents/fillers, binders, lubricants, desintegrants, coatings, preservants
and stabilizers, colorants and flavourings
Pharmaceutical dosage form
◦ is a drug delivery system which is formed by technological processing
(drug formulation)
◦ determines the physical form of the final pharmaceutical preparation
◦ must reflect therapeutic intentions, route of administrations, dosing etc.
Pharmaceutical preparation (PP)
◦ particular pharmaceutical product containing active and inactive
pharmaceutical ingredients formulated into the particular dosage form.
◦ Packed and labelled appropriately
9. Depending on the dosage form selected, various studies are
conducted to accomplish the goal. Formulations developed are
tested for both physical and chemical stability at accelerated
temperatures.
Evaluation Tests For Dosage Forms
Weight variation test
Drug Content
Stability
Dissolution
Skin Irritant Test
Viscosity
Clarity
10. Bioequivalence is a relative term which denotes that the drug
substance in two or more identical dosage forms reaches the
systemic circulation at the same relative rate and to the same
relative extent.
Bioequivalence studies are conducted by pharmacokinetic
method and pharmacodynamic method.
Types of bioequivalence studies:
1. In vivo Bioequivalence studies
2. In vitro Bioequivalence studies
11. 1. In vivo Bioequivalence studies
The following sequence of criteria is useful in assessing the need for in vivo
studies
Oral immediate release products with systemic action
Non-oral immediate release products
Modified release products with systemic action
2. In vitro Bioequivalence studies
The drug product has been slightly reformulated by the original
manufacturer
An acceptable In-vitro In-vivo correlation and the in vitro dissolution rate
of the new product is equivalent with that of the already approved
medicinal product
12.
•
•
Regulatory affairs (RA), also called government affairs, is a
profession within regulated industries, such as pharmaceuticals,
medical devices and energy.
The regulatory function in healthcare industries is vital in
making safe and effective healthcare products available
worldwide.
The (Healthcare) Regulatory Affairs Profession is still an
emergent profession but has two major international
professional membership societies:
The Regulatory Affairs Professionals Society (RAPS)
The Organisation for Professionals in Regulatory Affairs
(TOPRA)
13. Indian-CDSCO (central drug standard control organisation)
The CDSCO establishes safety, efficacy, and quality standards for pharmaceuticals
and medical devices. It publishes and updates the Indian Pharmacopeia, a list of
regulated pharmaceuticals and devices.
US-FDA (Food and Drug Administration)
FDA is responsible for protecting and promoting public health through the regulation
and supervision of food safety, tobacco products, dietary supplements, prescription,
cosmetics and OTC products.
Canadian-HPFB (The Health Products and Food Branch)
minimizing health risk factors to Canadians while maximizing the safety provided by
the regulatory system for health products and food;
Australian-TGA(The Therapeutic Goods Administration)
is responsible for regulating therapeutic goods including medicines, medical devices,
blood and blood products,
14.
Tablets - Compressed product (API+ excipients – e.g., fillers,
desintegrants)
◦ Conventional –Desintegration/Desagregation/Dissolution, can be
divided (half/quarters)
◦ Coated (not to be divided)
To mask unpleasant taste or smell of API
To avoid of adhesion in oesophagus (to facilitate swallowing and/or
avoid release of API and local adverse reactions)
To ensure drug stability
15.
Capsules
- API + excipients - enclosed in the hard/soft water soluble
container made of gelatin.
- Consist of cap and body – filled with powders, pellets, granules
(paste, oil)
- In the GIT gelatin shell softens, swells and dissolve particles
are dispersed → disintegration → API dissolution → absorption
- Hygroscopic
16.
Solutions (drops) – aqueous, oils
◦ Syrups – aqueous solutions with sugar (or sugar substitute)
with/without flavouring agents
◦ Elixirs – sweetened hydroalcoholic solutions which can
accomodate less water.
◦ Tinctures – alcoholic or hydroalcoholic solutions – herbal
extracts.
Emulsions-API+oil+water+emulsifying agent
Suspension –API+solvent+suspendig agent
- should not be used for drugs with high potency.
17. Semisolid dosage forms
1.Unshaped (without specific physical shape)
•Gels -A semisolid systems in which a liquid phase is constrained
within a 3D cross-linked matrix.
•Creams – semisolid emulsion systems (o/w, w/o) containing more than
10% of water.
o/w creams - more comfortable and cosmetically acceptable as they
are less greasy and more easily water washable
w/o creams – accommodate and release better lipophilic API,
moisturizing, Cold creams
•Ointments – semisolid dosage forms with the oleaginous
(hydrocarbon), water-soluble or emulsifying base
Oleaginous (hydrocabon) base: Petrolatum (Vaseline – white,
yellow)
Water-soluble base: Polyethylenglycol (PEG)- ointment , macrogol
ointments
•Pastes – semisolid dispersion system, where a solid particles (> 25%,
e.g. ZnO) are dispersed in ointments – mostly oleaginous (Petrolatum)
18. 2.Shapedsuppositories (for rectal administration)
-Solid dosage form under room temperature which are melted at
the body temperature.
-Different size & shapes– children and adult suppositories
-Chemically stable and inert.
-Oleaginous (cacao butter, adeps neutralis) or aqueous (PEGs,
glycerinated gelatine)
Gases dosage forms
1.Gases – medicinal gases, inhalation/volatile anaesthetics
(vaporised before administration by inhalation)
2.Aerodispersions of solid particles (e.g., inhalation
antiasthmatics) or liquid particles (inhalation antiasthmatics
or sprays)
19.
20.
21. The
above steps are to be followed to formulate an
efficient dosge form with maximum therapeutic
response and safety with minimum toxicity.
22. Theory &practice of Industrial pharmacy by Leon
lachman
Biopharmaceutics & pharmacokinetics by
D.M
Brahmankar
Physical pharmacy &pharmaceutical sciences by
Martn’s
