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DR. AJMAL NASIRDirector Technical

BF BiosciencesLAHORE

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Dosage Forms Or

Pharmaceutical Preparation

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Direct Clinical Use Of The Active DrugSubstances 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 thetherapeutically 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 highConcentrations at the site of administration.

API can have unpleasant organoleptic qualities(taste, smell)

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PHARMACEUTICALPREPARATION

API

EXCIPIEN

T

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API (Active pharmaceutical ingredient)

Excipient (Inactive Pharmaceutical Ingredients)Added for:TechnologicalBiopharmaceutical

Stability reasonsCommon excipient are:oDiluents / Fillers,Binders ,Lubricants ,DisintegrantsoCoatings ,Preservants,Stabilizers,Colorants ,Flavourings.

Pharmaceutical Dosage Form

Determines the physical form of the final pharmaceuticalpreparation. Is a drug delivery system result of technological processing

(drug formulation) Must reflect therapeutic intentions, Route of administrations,

Dosing etc.

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Pharmaceutical preparation (PP)Particular Pharmaceutical Product Containing

Active And Inactive Pharmaceutical IngredientsFormulated 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 andgeneric preparations)

B. Compounded individually in compoundingpharmacies

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Most frequent and favourable approach.

MUST be approved by national authority FDA, EU ,EMEAetc.

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.

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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 the original

preparation.

Must be pharmaceutically equivalent: same API, dose, pharmaceuticaldosage 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 ascompared with the original preparation.

Only Bioequivalance is required .Decrease the costs of pharmacotherapy and thus make the drugs more

available

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These PP are compounded individuallyFor a particular patientAccording to the physician's prescriptionPharmacy licensed for compounding.

Used rarely and in specific situations.

Commercially available PP should be preferred over thecompounding.

The main advantage is:Individualize the pharmacotherapycover all individual demands

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Individually compounded PP can be a justified as achoice when:

Particular dosage form is not commercially available on themarket

The extraordinary low or high dose is needed (youngchildren, elderly people, special situations e.g.,intoxications).Allergy on a specific excipients (e.g., lactose a filler, somecolorizing/flavouring or antimicrobial agents - parabens) or

another drug appearing in the PPThe major disadvantage is the lack of standardization (it isalways a single-patient batch), unavailability of rigorous

QC testing and the appropriate clinical evaluation.

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CLASSIFICATION OF PHARMACEUTICAL DOSAGE

FORMS ACCORDING TO ITS PHYSICAL PROPERTIES

DOSAGE FORMSA. Homogenous systems

B. Dispersion systemsa) one phase (dispersed phase) is distributed

throughout another one (continuous phase,dispersion medium)

b) According to the size of dispersed particles (1 nm-0,5 mm) a molecular, colloidal and coarsedispersions can be distinguished

c) May require shaking before administration

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According to the overall physical properties ofdosage forms (both homogenous and dispersionsystems) one can distinguish.

A. Gaseous dosage forms

B. Liquid dosage forms

C. Semisolid dosage forms

D. Solid dosage forms



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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

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

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

ow



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Volume/weight for estimation of dose of liquid

dosage forms

Dosing measureAprox. volume

(ml)

Aprox. weight

(g)

1 drop 0,05 0,05

1 teaspoonful 5 5

1 tablespoonful 15 15

20 drops of aqueous solution 1 1

60 drops of ethanolic solution 1,25 1

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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 constrainedwithin a 3D cross-linked matrix.

Creams semisolid emulsion systems (o/w, w/o) containing morethan 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)

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ShapedSuppositories (for rectal administration)

Different shapes

Melting/dissolving at body temperatureOleaginous (cacao butter, ) or aqueous (PEGs,glycerinated gelatine)

Pessaries (vaginal suppositories)Similar as above, PEGs or glycerinated gelatine areoften used as base.



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SOLID DOSAGE FORMSUnshaped (without specific shape)

Powders for external/internal use

Shaped Tablets Capsules Implantates Transdermal patches



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according to the ROUTE OF ADMINISTRATION

FOR SYSTEMICADMINISTRATION

Oral Sub lingual and

Buccal .

Rectal

Parenteral

Transdermal Inhalation

FOR LOCALADMINISTRATION

Topical (on the skinor mucosa) Into/onto - the eye,

nose, ear

The Oral cavity

The vagina, Rectum The brochi

The skin

DOSAGE FORMS

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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

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CONVENTIONAL VS. CONTROLLED RELEASE

DOSAGE FORMS

I. Genrtaion ( conventional)

Disintegration (

desegregation) of the dosageform and dissolution of APIis spontaneous process;

Drug absorption and

distribution is based only onphysico-chemical propertiesof API

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II. Genration (SR & CR)

. The release of API is under control ofthe drug delivery system (temporalcontrol)

Advantages:Avoids fluctuations of plasma drug

concentration better safety andefficacy

Decreased frequency of drugadministration (often once dailyadmin) better complianceMay overcome some problems withBAVCan be much more economical

(better cost-effectiveness)Sustained release (SR) release ofthe initial API dose & further

prolonged releaseControlled release (CR) properlycontrolled (0. order) release of API

Pulsatile release

CONVENTIONAL VS. CONTROLLED RELEASE

DOSAGE FORMS

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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 isreleased continuously

Polymer matrix can form pore drug can gradually

diffuse

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SOLID DOSAGE FORMS

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DRUGDOSAGEFORMS

SOLIDDOSAGEFORMS

LIQUIDDOSAGEFORMS

SEMI-SOLIDDOSAGEFORMS

OTHERSNASAL

INHALATION

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SOLIDDOSAGEFORMS

TABLETSCAPSULES LOZENGES POWDERS

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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

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SOLID DOSAGE FORMS

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SOLID DOSAGE FORMS

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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

SOLID DOSAGE FORMS

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