DR.

AJMAL NASIR
Director Technical BF Biosciences LAHORE

Dosage Forms Or Pharmaceutical Preparation

Direct Clinical Use Of The Active Drug Substances As They Are Is Rare Due To The Number Of Good Reasons:
API handling can be difficult or impossible (e.g., low mg and g doses) Accurate drug dosing can be difficult or impossible. API administration can be impractical, unfeasible or not according to the therapeutically aims. Some API need to be chemically stabilised due to the inherent chemical instability. API can be degraded at the site of administration (e.g., low pH in stomach). API may cause local irritations or injury when they are present at Concentrations at the site of administration. API can have unpleasant organoleptic qualities(taste, smell) high

API

EXCI PIEN T

PHARMACEUTICAL PREPARATION

API (Active pharmaceutical ingredient) Excipient (Inactive Pharmaceutical Ingredients) Added for:

Technological Biopharmaceutical Stability reasons Common excipient are: o Diluents / Fillers,Binders ,Lubricants ,Disintegrants o Coatings ,Preservants,Stabilizers,Colorants ,Flavourings.

Pharmaceutical Dosage Form

Determines the physical form of the final pharmaceutical preparation. Is a drug delivery system result of technological processing (drug formulation) 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.

Two major types of PP according the origin:

A. Manufactured in large scales by pharmaceutical industry (original and generic preparations) B. Compounded individually in compounding pharmacies

Most frequent and favourable approach. MUST be approved by national authority FDA, EU ,EMEA etc. Rigorous quality control (QC) and quality assurance (QA) during manufacturing for safety and effectiveness.

ORIGINAL PHARMACEUTICAL PREPARATIONS

Undergo full and very extensive pharmacological/toxicological and pharmaceutical pre-clinical and clinical development and evaluation. Effectiveness and safety is approved.

GENERIC PHARMACEUTICAL PREPARATIONS

(Authorised copies of original preparations)
After the expiration of the patent protection of the original preparation. The approval is easier due to the prior experience with preparation. the original

Must be pharmaceutically equivalent: same API, dose, pharmaceutical dosage form and the same route of administration as in original preparation. Must be clinically bioequivalent: i.e. it must be of very close PK profile as original preparation. PK parameters (Cmax, tmax, AUC) are within 80-125 % range as compared with the original preparation. Only Bioequivalance is required . Decrease the costs of pharmacotherapy and thus make the drugs more available

These PP are compounded individually

For a particular patient According to the physician's prescription Pharmacy licensed for compounding.

Used rarely and in specific situations.

Commercially available PP should be preferred over the compounding. The main advantage is:
Individualize the pharmacotherapy cover all individual demands

Individually compounded PP can be a justified as a choice when:

Particular dosage form is not commercially available on the market The extraordinary low or high dose is needed (young children, elderly people, special situations e.g., intoxications). Allergy on a specific excipients (e.g., lactose a filler, some colorizing/flavouring or antimicrobial agents - parabens) or another drug appearing in the PP

The major disadvantage is the lack of standardization (it is always a single-patient batch), unavailability of rigorous QC testing and the appropriate clinical evaluation.

CLASSIFICATION OF PHARMACEUTICAL DOSAGE FORMS ACCORDING TO ITS PHYSICAL PROPERTIES

DOSAGE FORMS A. Homogenous systems B. Dispersion systems
a)

b)

c)

one phase (dispersed phase) is distributed throughout another one (continuous phase, dispersion medium) According to the size of dispersed particles (1 nm0,5 mm) a molecular, colloidal and coarse dispersions can be distinguished May require shaking before administration

CLASSIFICATION OF PHARMACEUTICAL DOSAGE FORMS ACCORDING TO ITS PHYSICAL PROPERTIES

According to the overall physical properties of dosage forms (both homogenous and dispersion systems) one can distinguish.
A. Gaseous dosage forms B. Liquid dosage forms C. Semisolid dosage forms

D. Solid dosage forms

CLASSIFICATION OF PHARMACEUTICAL DOSAGE FORMS ACCORDING TO ITS PHYSICAL PROPERTIES

Gases
Gases medicinal gases, inhalation/volatile anaesthetics (vaporised

before administration by inhalation) Aerodispersions of solid particles (e.g., inhalation antiasthmatics) or liquid particles (inhalation antiasthmatics or sprays)

Liquids
Solutions one homogenous phase, prepared by dissolving one or

more solutes in a solvent Emulsions

Suspensions A dispersion system where solid particles are dispersed in liquid phase Not intended for systemic administration of drugs with high potency

a dispersion system consisting of two immiscible liquids o/w or w/o o cloudy appearance w

Volume/weight for estimation of dose of liquid dosage forms

Dosing measure
1 drop 1 teaspoonful

Aprox. volume (ml) 0,05 5

Aprox. weight (g) 0,05 5

1 tablespoonful
20 drops of aqueous solution

15
1

15
1

60 drops of ethanolic solution

1,25

Classification of pharmaceutical dosage forms according to its PHYSICAL PROPERTIES

SEMISOLID DOSAGE FORMS
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 syn. macrogol ointments Pastes semisolid dispersion system, where a solid particles (> 25%, e.g. ZnO) are dispersed in ointments mostly oleaginous (Petrolatum)

Classification of pharmaceutical dosage forms according to its PHYSICAL PROPERTIES

Shaped

Suppositories (for rectal administration) Different shapes Melting/dissolving at body temperature Oleaginous (cacao butter, ) or aqueous (PEGs, glycerinated gelatine)
Pessaries (vaginal suppositories) Similar as above, PEGs or glycerinated gelatine are often used as base.

Classification of pharmaceutical dosage forms according to its PHYSICAL PROPERTIES

SOLID DOSAGE FORMS Unshaped (without specific shape)

Powders for external/internal use

Shaped

Tablets Capsules Implantates Transdermal patches

Classification of pharmaceutical dosage forms according to the ROUTE OF ADMINISTRATION

DOSAGE FORMS
FOR SYSTEMIC
FOR LOCAL

ADMINISTRATION Oral Sub lingual and Buccal . Rectal Parenteral Transdermal Inhalation

ADMINISTRATION Topical (on the skin or mucosa)

Into/onto - the eye, nose, ear The Oral cavity The vagina, Rectum The brochi The skin

Pharmaceutical dosage forms for systemic administration

Generations of dosage forms
1st gen. conventional (unmodified) release of API
2nd gen. controlled release of API (CR) 3rd gen. targeted distribution drug delivery systems

CONVENTIONAL VS. CONTROLLED RELEASE DOSAGE FORMS

I. Genrtaion ( conventional) Disintegration (

desegregation) of the dosage form and dissolution of API is spontaneous process;

Drug absorption and

distribution is based only on physico-chemical properties of API

CONVENTIONAL VS. CONTROLLED RELEASE DOSAGE FORMS

II. Genration (SR & CR) . The release of API is under control of the drug delivery system (temporal control) Advantages:
Avoids fluctuations of plasma drug concentration better safety and efficacy Decreased frequency of drug administration (often once daily admin) better compliance May overcome some problems with BAV Can be much more economical (better cost-effectiveness)

Sustained release (SR) release of the initial API dose & further prolonged release Controlled release (CR) properly controlled (0. order) release of API Pulsatile release

CR (SR) TABLETS AND CAPSULES

Reservoir Type (not to be divided)

Core consisting of API Excipients is encapsulated by wall/membrane determining the rate of release

Mechanisms of release

Dissolution of the outer/inner layer Diffusion (permeation) throughout membrane pores Osmosis (OROS system)

Matrix Type (tablets)

Drug is dispersed within the polymer

Polymer matrix can be biodegradable drug is released continuously Polymer matrix can form pore drug can gradually diffuse

SOLID DOSAGE FORMS

DRUG DOSAGE FORMS SOLID DOSAGE FORMS LIQUID DOSAGE FORMS SEMI-SOLID DOSAGE FORMS OTHERS NASAL INHALATION

SOLID DOSAGE FORMS CAPSULES TABLETS LOZENGES

POWDERS

SOLID DOSAGE FORMS

Capsules,

Sustained-release capsules,
Tablets, Pills, Are used to divide a drug or mixture of drugs into definite doses and avoid the inconvenience of preparing the dose from dry powders. Tablets are a convenient way of giving drugs that have an unpleasant taste

SOLID DOSAGE FORMS

SOLID DOSAGE FORMS

SOLID DOSAGE FORMS

CAPSULES
The most popular dosage forms for the oral administration of

powders, oils, and liquid Dissolve readily in the stomach and make the contents available for absorption only slightly less quickly than a liquid medicament Not to be divided, can also be compounded individually). API + excipient - 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 Enteric coating available