1. PHARMACEUTICAL EXCIPIENTS
Course : Pharmaceutical Microbiology
Course ID: MIC 306
Fahareen-Binta-Mosharraf
MNS

2. Excipients – an overview
Drug products contain both drug substance (commonly referred to as Active pharmaceutical ingredient or API) and Excipients.
The resultant biological, chemical and physical properties of the drug product are directly affected by the excipients chosen, their concentration and interactions with the API
Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation.
Certain excipients can have different functional roles in different formulation types,
e.g. lactose; widely used as:
a diluent, filler or bulking agent in tablets and capsules

3. Introduction
Overview of excipients commonly used (particularly in oral dosage forms)
Tablet Excipients
Diluents (fillers, bulking agents), Disintegrants, Binders, Lubricants, Glidants
Liquid/Suspension Excipients
Solvents/co-solvents , Buffering agents, Preservatives, Anti-oxidants, Wetting agents, Anti-foaming agents, Thickening agents, Sweetening agents, Flavouring agents
Paediatric considerations with regard to excipients

4. API (Active Pharmaceutical Ingredients)
Active Pharmaceutical Ingredients (API) (or) Drugs (meant for oral administration) are classified into two types based on their solubility:
a). Insoluble drugs.
b). Soluble drugs.
a). Insoluble drugs : The therapeutic action of insoluble drugs depends on the surface properties of the drug particles i.e., fine particle size and larger surface area.
Eg: Antacids
b). Soluble drugs : The therapeutic action of soluble drug is seen systemically. The disintegration and dissolution time of such tablets depends upon the excipients used in the formulation.
Example: paracetamol, aspirin

5. Function of Excipients

6. Excipients

7. Diluents
Diluents : Act as fillers used to make required bulk of the tablet. Diluents are used to increase the bulk content of the dosage form
For e.g. if the active ingredient is just 5 mg, is such a case a tablet of just 5 mg is very difficult to manufacture and handle too, thus the bulk content is increased by addition of inactive excipient. Must provide better tablet properties such as improved cohesion, to permit the use of direct compression manufacturing or to promote flow.
A diluent should have following properties:
Non toxic.
Commercially available in acceptable grade.
Low in cost. Physiologically inert.
Physically & chemically stable by themselves & in combination with the drugs.
Free from all microbial contamination.
Should not alter the bioavailability of the drug .
Colour compatible.

8. Commonly used tablet diluents
Diluents Based on Chemical nature Solubility Organic diluents Inorganic diluents Water soluble diluents Water Insoluble diluents. For e.g.
Lactose-anhydrous and spray dried lactose
Hydrolyzed starch
Microcrystalline cellulose
Mannitol
Sorbitol
Sucrose

9. Binders
These are the dry powders or liquid which are added during wet granulation to promote cohesiveness
It provides mechanical strength to the tablet.
Binders can be in powder form and liquid form.
Example of binders are
Powder binders : cellulose, methyl cellulose
Solution binders : gelatine, PEG, sucrose, starch

10. Disintegrants
Disintegrants are added to the formulation as it breaks the dosage form into smaller particles when it comes in contact with the liquid, these smaller fragments have greater surface area which will increase the dissolution of the drug.
Various mechanism of disintegrations are proposed-
Repulsion(By breaking into fragments): When the tablet comes in contact with the liquid, the liquid penetrates into the pores of the tablets and breaks it into fragments.
Deformation (By swelling): when the tablet comes in contact with the water it swells and ruptures the tablet into small particles.
Examples of disintegrants are: starch, starch derivatives, cellulose,

12. Excipient –Functional Subclass
Excipients are sub-divided into various functional classifications, depending on the role that they play in the resultant formulation.
In Liquid/Suspension products, the possible types of excipients include:
Solvents/co-solvents e.g, Glycerol
Buffering agents, e.g., Lactates
Preservatives, e.g. Na Benzoate, Parabens (Me, Pr and Bu), BKC
Anti-oxidants, e.g. Ascorbic acid
Wetting agents, e.g. Polysorbates, Sorbitan esters
Anti-foaming agents, e.g. Simethicone
Thickening agents, e.g. Methylcellulose or Hydroxyethylcellulose
Sweetening agents, e.g. Sorbitol, Saccharin, Aspartame
Flavouring agents, e.g. Peppermint, Lemon oils, Butterscotch, etc.

13. Sweetening Agents Natural sweeteners Artificial sweeteners
Sucrose; soluble in water (vehicle), colourless, stable (pH 4-8), increases viscosity;
Sorbitol (non-cariogenic, non-calorific - appropriate for paediatric formulations), but lower sweetness intensity than sucrose (so you need more) & can cause diarrhoea
Artificial sweeteners
Can impart a bitter or metallic after-taste (hence used in combination with natural sweeteners), e.g.
Saccharin, and it’s salts
Aspartame
Sucralose – excellent sweetness, non-cariogenic, low calorie, wide & growing regulatory acceptability but relatively expensive

14. Solvents/Solvent sweeteners
Need for oral liquid preparations (that children typically find easier to swallow) often necessitates:
Most commonly used solvent sweeteners are
Propylene glycol
Glycerine (Glycerol)

15. The Ideal Preservative
Is free of toxic or irritant effects at the concentrations used.
Is effective in preventing the growth of micro-organisms most likely to contaminate the preparation.
Is sufficiently soluble in water to achieve adequate concentrations in the aqueous phase of a system of two or more phases.
Has adequate stability to heat and prolonged storage, with no chemical decomposition
Is chemically compatibility with all other formulation components
Has an acceptable odor and color.
Is cheap

16. Examples of chemical preservatives used in pharmaceutical products
Injectables      Benzalkonium chloride      Chlorocresol      Phenol
Ophthalmic      Phenylethanol      Chlorohexidine      Thiomersal
Topical / Oral      Benzoic acid      Parabens      Sorbic acid

17. Preservatives Toxicity
Propylene Glycol Toxicity
Propylene glycol is a general solvent and antimicrobial preservative used in a wide range of pharmaceutical preparations including oral liquid, topical preparations
However, it’s use in large volumes in children is discouraged:
PG has been associated with cardiovascular, hepatic and CNS adverse events, especially in neonates (where the biological half-life is prolonged (~17h) compared with adults (5h)).

18. Preservatives
Benzyl Alcohol toxicity in neonates
Widely used as a preservative in cosmetics, foods and pharmaceuticals (including injectables and oral liquids)
Toxic syndrome observed in neonates
Dilution of nebulisation led to severe respiratory complications and even death in neonates

19. Lactose toxicity (immature metabolism)
In pharmaceutical preparations it is widely used as a diluent in tablets and capsules, in lyophilised powders, as a sweetener in liquid formulations and as a carrier in dry powder inhalation products.
Lactose intolerance occurs when there is a deficiency in the intestinal enzyme lactase, leading to GIT build-up of lactose. There is then the risk of abdominal bloating and cramps.

20. Types of dosage forms:
Definition: Dosage forms are the means by which drug molecules are delivered to sites of action within the body.
They are classified according to:
Route of administration Physical form
Oral Solid
Topical Semisolid
Rectal liquid
Parenteral
Vaginal
Inhaled
Ophthalmic
Otic

21. The Need for Dosage Forms
To protect the drug substance from the destructive influences of atmospheric oxygen or humidity. (Coated tablets)
To protect the drug substance from the destructive influence of gastric acid after oral administration. (Enteric-coated)

22. The Need for Dosage Forms
To conceal the bitter, salty or offensive taste or odor of a drug substance. (Capsules, Flavored syrups)
To provide liquid preparations of substances that are either insoluble or unstable in the desired vehicle. (Suspension)

23. A capsule is a medication in a gelatin container.
- The two main types of capsules are:
1- hard-shelled capsules, which are normally used for dry, powdered ingredients,
2- soft-shelled capsules, primarily used for oils and for active ingredients that are dissolved or suspended in oil.

24. The Need for Dosage Forms
To provide placement of drugs directly in the bloodstream or body tissues (Injections)
To provide for optimal drug action through inhalation therapy (Inhalants, Inhalation aerosols)