Dosage Forms and Routes of Drug Administration

Drugs are not used as pure chemical substances but are given in formulated preparations.

These are to attain a desirable therapeutic response (bioavailability), patient convenience and acceptability to treat disease, to ensure chemical and physical stability, and uniformity of dosage form. 

Definition

Dosage forms are the means by which Active Pharmaceutical Compounds are made for the desired pharmacokinetic site of drug action to optimize maximum effect of active compounds with the minimization of adverse effects. There are numerous dosage forms into which a drug substance can be incorporated for the convenient and efficacious treatment of a disease.

Classification of Dosage Form on the Basis of Physical Properties

The dosage form can be classified into four different categories:

• Solid Dosage Form
• Liquid Dosage Form
• Semisolid Dosage Form
• Gases Dosage Form

Table: Classification on the basis of physical properties

Classification of Dosage Form on the Basis of Administration

The dosage form can be designed for administration by all possible delivery routes to enhance the therapeutic response. Solid, Liquid and Semisolid dosage forms can be taken either orally or injected, as well as being applied to the skin or inhaled.

Route of Administration

Enteral Administration

The central route of administration involves gastrointestinal route for drug metabolism. This type of administration is for the drug that needs GI Tract for drug absorption and metabolism.

• Oral Route

The route of administration in which the dosage form is taken via mouth, intended for systemic effects from drug absorption from various mucosal membranes of gastrointestinal tract. This route of administration is the most common, simplest and safest; mainly aimed for the patient who is conscious. The most popular oral dosage forms are tablets, capsules, suspensions, solutions, syrup and emulsions. The specific disadvantage of this route is first-pass metabolism in the liver.

• Sublingual Route

Sublingual route bypasses the first-pass metabolism i.e. enters systemic circulation directly and has rapid onset of action. Generally drugs are placed under the tongue for rapid absorption and are favorable for emergency medication, for example nitroglycerin, isoproterenol hydrochloride or erythrityl tetranitrate. The major disadvantage of this route is to cause irritation in the oral mucosa.

• Buccal Route

Buccal Route also bypasses the first-pass metabolism and aims for local effect in buccal cavity. Absorption takes place via cheek mucosa and relatively shows sustained release effect. For example, buccal tablets (progesterone), lozenges (vicks, strepsils) and dental cones.

Topical and Transdermal Delivery Systems

Topical drugs are applied on the outer layer of skin, mainly for local action. In this route of administration sweat gland, hair follicles, sebaceous glands and stratum corneum are involved for drug absorption. Creams, ointments and pastes are the most common topical dosage forms. However, for hormonal therapy and chronic conditions, transdermal delivery systems are widely used. 

Inhalation and Pulmonary Drug Delivery

Inhalation and pulmonary drug delivery systems are via respiratory tract (covers large surface area of the mucous membrane of respiratory tract and pulmonary epithelium) and include solutions or suspensions delivered by drops or fine aerosol from a spray. Drug particles are mostly in the form of gases or in an aerosol. Thus, this delivery route has been found particularly useful for rapid onset of action covering large surface area for action in the lungs. For example, corticosteroids like fluticasone, inhaled anesthetics, powdered aerosols (sodium cromoglycate), metered aerosols, etc. to patients.

Rectal and Vaginal Administration

Solutions, suppository or emulsion are administered rectally for local effects rather than systemic effects. This route is useful for the drug that gets inactivated by the liver or by the gastrointestinal fluid. Mostly drugs that are administered orally can also be administered rectally as a suppository. Suppositories are solid forms intended for introduction into body cavities (usually rectal, but also vaginal and urethral) where they melt, releasing the drug whereas enemas are liquid solutions used to treat constipation.

Vaginal tablets are typically ovoid or pear shaped for ease of insertion and is meant to dissolve slowly in the vaginal cavity. These tablets are generally used to release steroids or antimicrobial agents.

Irregular drug absorption is the disadvantages of both rectal and vaginal route of administration.

Ophthalmic and Otic Preparations

Ophthalmic route is the administration of drugs to the eyes. For example: eye drops, eye ointments, gel etc. The ophthalmic preparation needs to be sterile to prevent the sensitive and delicate tissue of the eyes from infection, vision damage or blindness.  

Otic route is for nasal dosage form such as solution, suspension delivered via drops or fine aerosol from a spray. They are generally viscous in nature to prolong contact with affected areas.

Parenteral Administration

The word parenteral is a Greek word i.e. “Para” means outside and “enteron” means intestine. Parenteral administration involves direct engagement of systemic circulation via bodily tissues. In emergency situations and patients noncompliance to oral medication the parenteral route of drug administration is more favorable.  A hollow needle is used to deliver drugs to targeted sites with varying depth of penetration. Parenteral routes are mainly of three types: intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) but other specialized routes are intra-arterial (artery), intracardiac (heart), intra articular (joints), intraspinal (spinal column), intrasynovial (joint fluid), intrathecal (spinal fluid), intracerebral (brain), etc. Parenteral administration is ideal when rapid action or precise dosing is required. These types of dosage forms are sterile and packed in a form that ensures the retention of sterility.

• Intravenous (IV)

Intravenous is a routine route of drug administration in clinics or hospitals where drugs are administered directly into the systemic circulation either by direct injection or by infusion. Bioavailability of IV route is 100% with immediate onset of action. Intravenous injections are given at 25 degree angle to the skin into the superficial veins.

• Intramuscular (IM)

Intramuscular injections are given at a 90 degree angle to the skin into deep skeletal muscle far from blood vessels and nerves. Sites of administrations are Gluteal site, Vastus Lateralis muscle, Rectus femoris muscle and Deltoid muscle. Mode of absorption is intermediate but has a longer duration of action due to formation of ‘depot’. The scariest part of the IM route is its adverse effects such as paralysis, abscess, cysts, embolism, etc.

• Subcutaneous (SC)

Subcutaneous injections are given by pinching at least 1 inch fold of skin and tissue by holding the needle at 45 degree angle to the skin into loose connective tissue between the dermis and the muscle layer. The site of subcutaneous injection is abdomen, upper- outer arms, upper- outer thighs and upper back. This type of administration is common for insulin and vaccines. Drug absorption is slow but sustained.

Novel Drug Delivery Systems (NDDS)

Novel Drug Delivery system is a modified version of Conventional Drug Delivery system which alleviates the drawbacks of Conventional Drug Delivery System. NDDS sets the new strategy, technology, methodology and formulations for a safe administration at a site of action within the body, where drug plasma level is maintained for a specific dose in a safest way for a predetermined duration of action. NDDS improves drug potency, drug stability, control release, targeted dispersion and patient satisfactory compliance.

NDDS governs the new technologies such as nanoparticles, liposomes, micro-needle patches, microencapsulation or implantable devices. The advantage of NDDS offers:

• Targeted drug release: Decreases toxicity by lowering the dosage needed for the desired therapeutic effect.
• Decreases dosing frequency: Due to sustained release/ controlled release of drug
• Enhances bioavailability: By improving solubility, permeability, dissolution and protection of drug substance.
• Improves Patient Compliances: By reduction in dosing frequency, minimizing side effects and convenient administration.
• Chronic disease management: These systems provide long acting formulations that deliver the drug over an extended period of time
• Gene and cell therapy: Different NDDS provides gene and cell therapy by delivering genetic material or therapeutic cells to specific sites for targeted and efficient therapy. NDDS protects the gene/cell from deterioration.

Major approaches which are applied for NDDS:

• Carrier Based Drug Delivery System

Carrier Based Drug Delivery System is a technique of NDDS in which specific carriers are used to enhance the selectivity, efficacy, and safety of drug delivery. These carriers aim to improve the solubility, stability, efficacy and transport of drugs to specific target sites which leads to specific therapeutics outcomes.

Carriers used in carrier based drug delivery systems help to encapsulate medications in form of Nanoparticles, Microspheres, Liposomes and Niosomes etc. These carrier forms help to transfer drugs to certain locations inside the body, enabling controlled release and sustained drug profile. 

• Liposomes: Example of Targeted Delivery

Liposomes are made up of one or more lipid bilayers surrounding the internal aqueous compartment. If the drug is hydrophilic, it gets attached to the inner compartment and to the liposomal membrane. 

• Microspheres and Nanoparticles: 

These delivery systems help to formulate long acting depots, cosmetic preparation and helps in bypassing the biological barriers.

• Ganciclovir Implant: Example of  Localized Delivery
• Transdermal Drug Delivery System: Transdermal Drug Delivery System involves skin; delivers drugs to systemic circulation through skin in the form of Microencapsulation, Osmotic pump and Sonophoresis at a specific rate in a controlled manner over a prolonged period of time. This delivery system helps to maintain therapeutic window and minimize side effects of a drug.

• Microencapsulation: Solid, liquid or gases drug particles are incorporated in the coating of polymeric microcapsules. This method helps in easy handling and concealing the active compound allowing for precise dose distribution.
• Osmotic Pump: Example of Constant Release

It has reservoir-like design in which a dosage form has a hole of 0.4mm covered by a semipermeable membrane which has a drug layer and a polymeric osmotic layer. In contact with water in a patient’s stomach, an osmotic agent draws water from the surrounding through a semipermeable membrane and drug starts to release until the osmotic gradient remains constant.

• Matrix System: Example of Sustained Release

Factors Influencing the Choice of Route

The different choices of route are discovered in order to overcome the limitation of site of administration. The right route ensures high therapeutic benefits diminishing the adverse effects. Some of the factors influencing the choice of administration are-

• Nature and Stability of drugs: Physical and chemical properties of drug such as solid/ liquid/ gas; solubility, stability, PH, irritancy site of desired action (local/generalized)
• Effects of digestive juices and First pass metabolism
• Bioavailability: Rate and extent of absorption from various site
• Patient’s age, compliance and condition
• Cost and Convenience
• Desired onset of action: Emergency/routine

Conclusion

Dosage form and route of administration have a crucial role in drug quality, safety and efficacy. From the development of Conventional Dosage Form to modern technology of Novel Drug Delivery systems the therapeutic value, bioavailability, rational drug use and patient compliances have been alleviated to meet patient needs. These concepts have enhanced clinical decision- making of drug development.

References

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