Drug Formulatio

ns &

Routes of Administrat

ionMa. Minda Luz M. Manuguid, M.D.

General Considerations

• Pharmaceutics – branch of Pharmacy that deals with drug formulations

• Pharmaceutical products need to be presented in a form that can be administered to an organism

• Formulation takes into consideration easy delivery as well as guaranteed desired action (drug reaches target, achieves therapeutic action)

Oral Preparations

Pill – round or ovoid solid body; may be coated with sugar or other substance

• Tablet – granulated powder containing one or more medications, compressed into a disc; must disintegrate in the GIT, so starch is often incorporated; + sugar-/film- coating;

• Dragees – chewable tablets• Enteric-coated tablets – coated with a

substance that is stable at acidic pH (will not disintegrate in the stomach) but breaks down rapidly at higher pH (small intestines)

Oral Preparations• Capsule – an outer “shell” holds the

drug inside– Hard gelatin capsule – contains solid drug in powder

form; may be opened– Soft gelatin capsule – contains the drug in liquid or semi-

liquid form; cannot be opened; useful for drugs that are insoluble in water

• Sustained/Slow-release preparations – drug is formulated in such a way that it releases very slowly in the GIT; a single dose suffices for delivery of the drug over a period of hours, ensuring sustained action.

Oral Preparations

Liquid preparations – for children & for adults who have difficulty swallowing pills; usually flavored to make them palatable;

• Elixirs – drugs insoluble in water are dissolved in Alcohol

• Syrups – sugared liquid preparations• Suspension – drug in solid form, not

dissolved in Alcohol• Emulsion – drug in liquid form, not

dissolved in Alcohol

Topical Preparations

Topical – application of a drug to the skin/ mucosa overlying the area to be treated

• Drops – isotonic solutions – ophthalmic, nasal, otic (eardrops – formulated as oily solutions for adherence to the aural cavity)

• Creams – water-based, poorly absorbed; drug is left on skin surface as water evaporates

• Ointments – lipid-based, greasy appearance & feel; drug penetrates deeply into tissues, especially if with “occlusive” dressing

• Pastes – have a very high powder content; water-repellent.

• Gels & Lotions – used on hairy parts of the body.

Drug preparations

Topical Preparations• Intranasal sprays – often

metered to deliver precise doses of the drug; can be absorbed systemically

• Transdermal patches – useful for administering lipophilic drugs & those that are active in very small amounts

• Suppositories – useful in nauseous or vomiting patients, unconscious patients, patients with difficulty of swallowing; may be administered rectally or vaginally (Pessaries)

Parenteral Preparations

Routes of Administration

• Oral• Sublingual • Mucosal• Transderm

al• Rectal• Vaginal

• Subcutaneous• Intramusclar• Intravenous • Intrathecal• Intra-articular• Epidural

Routes of Administration

Oral• most convenient, most economical• rate & extent of absorption

determines onset of drug action/effect• usual site of absorption: small

intestines• nonionized lipid-soluble forms favor

absorption– weak acids are highly ionized in small intestinal alkaline pH– weak acids are readily absorbed in the stomach

Oral administration• First pass effect:

– Drugs absorbed from the GIT passes through the portal venous system, then through the liver before finally reaching the systemic circulation, to the receptors & target tissues

– Extensive hepatic metabolism/extraction results in minimal drug delivery to the systemic circulation (e.g.propranolol,Demerol, INH)

– poor liver extraction, ↑bioavailability e.g. diazepam, warfarin• Disadvantages

– emesis due to GIT irritation– destruction of drug by gastric acid/ GI enzymes– unreliable or inconsistent absorption– metabolism of drug by intestinal flora

Sublingual administration

• Sublingual literally means 'under the tongue'. It is a method of administering substances by placing the medication under the tongue to gain rapid and direct entry into the blood vessels rather than via the digestive tract. Medically, sublingual drug administration is applied in the field of cardiovascular drugs. 

• sublingual drugs : Calcibloc, Nitroglycerin, Polypeptide K,

• comes in contact with the mucous membrane, or buccal mucosa, it diffuses into the epithelium beneath the tongue, the sublingual areas act like a blotting paper, readily soaking up the substance. This region contains a high density of blood vessels, and as a result, via osmosis, the substance quickly enters the blood stream at the sublingual artery and thereafter, polypeptide-k ® is carried by blood flow to the connected lingual artery. 

• Can all substances be administered sublingually? Not all substances are permeable and accessible to the buccal mucosa. In order for a nutrient to be effectively absorbed sublingually, it needs to be able to travel accross the buccal mucous membranes; by a process of diffusion known as osmosis and factors, such as pH, molecular weight, and lipid solubility of a substance may determine whether the route is possible.

Mucosal

Transdermal administration

Advantages• Sustained therapeutic plasma levels• Reliable drug absorption

– Molecular wt < 1000– pH range 5 – 9 in aqueous medium– No histamine-releasing action– Daily drug requirement < 10 mg

• Smaller doses, so lower incidence of side effects

• Generally good patient compliance• Examples: scopolamine, nitroglycerin,

nicotine, methylphenidate (or ADHD)

Rectal administration

• Proximal rectum administration – absorption into superior hemorrhoidal veins portal venous system - liver - systemic circulation

• Low rectal administration – entry into the systemic circulation without passing through the liver

• Generally unpredictable pharmacological responses

• Rectal mucosal irritation possible• Examples: antipyretics, anticonvulsants

Parenteral Administration

Parenteral – mode of drug administration that avoids the GIT. Drug injections. Use of ASEPTIC TECHNIQUE very very important!!

• Intravenous (IV) injections – fast action due to avoidance of GI absorption

• Intradermal – injected into the dermis; very slow absorption; only small quantities of the drug can be given this way.

• Subcutaneous – just beneath the skin; very slow route; poor blood supply

• Intramuscular – into the fleshy part of the muscle: gluteus, deltoid, anterior thigh;

Intravenous administration

Parenteral administration• Intravenous, Intramuscular,

Subcutaneous,• Ensures active drug absorption• More rapid drug delivery than Oral• Only route acceptable for unconscious

patients, uncooperative patients• Systemic absorption depends on

capillary membrane surface area, drug solubility in interstitial fluid

• Advantages:– Rapid precise blood drug levels– Irritant drugs more comfortably administered– Drug is rapidly diluted

Specialized Modes of Administration

• Intrathecal – drug is introduced into the CSF-filled space surrounding the spinal cord; for giving of drugs directly into the CNS, avoiding the blood-brain barrier e.g. Baclofen, Morphine

• Epidural – drug is introduced into the space above the dura; useful in administering local anesthetics for surgical procedures in the pelvic area & below

• Intra-articular – injection directly into joint spaces