Semisolid Dosage Forms & Percutaneous Absorption Principles

• The course focuses on the structure and function of the skin.
• The course also covers basic principles of diffusion and factors affecting percutaneous absorption
• Enhancement of skin penetration, TDDS are also covered.
• Manufacturing of semisolid dosage forms, cosmetic products, applications of aerosols and suppositories will be taught.

Competencies

• Define semisolid, transdermal, inhaled, and molded solid pharmaceutical dosage forms.
• Illustrate the role of pharmaceutical excipients in different dosage forms including terms, symbols and abbreviations.
• Compare different types of pharmaceutical dosage forms.
• Illustrate principles of formulations, physicochemical properties and quality control tests.
• Explain advantages/limitations of dosage forms and cosmetic preparations.
• Solve pharmaceutical calculations
• Justify pharmaceutical techniques and excipients.
• Explain the relation between physicochemical properties of materials and the design of dosage forms and drug bioavailability.
• Apply pharmaceutical knowledge in the formulation of safe, stable and effective dosage forms.
• Retrieve information from different sources to improve professional competencies.
• Demonstrate critical thinking, problem solving and decision making abilities.
• Being able to formulate independently different pharmaceutical dosage forms.

Assessment

• Theoretical assessment weighting: Quizzes & activities 30%, Midterm Exam 30%, Final Exam 40%.
• Practical assessment weighting: Laboratory work and report 15%, Project "practical work and presentation" 15%, Midterm Exam 30%, Final Exam 40%.

Lecture Outline covers

• Structure of the skin
• Functions of the skin
• Routes for drugs penetration through the skin
• Rationale approach to topical formulations
• Types and definitions of topical and transdermal dosage forms
• Semi-solid preparations for application to the skin

Skin Structure and Layers

• The skin consists of the epidermis, dermis, subcutaneous tissue, and skin appendages.
• The epidermis is a non-vascular multilayered structure with varying thickness.
• Keratinocytes, the principle epidermal cells, are lipophilic.
• Cells divide, producing the stratum corneum/horny layer
• (Stratum corneum is fully keratinized impermeable dead cells.)
• Dermis: connective tissue (elastic) formed from fibrous proteins in a semi-gel matrix of mucopolysaccharide.
• Nerves, blood vessels, and lymphatics traverse the dermis.
• The blood supply quickly absorbs compounds passing the epidermis.
• Subcutaneous Tissue: primarily a network of fat cells that acts as a shock absorber and thermal barrier.
• Skin Appendages: Sweat glands regulate body temperature and waste removal, while hair follicles with sebaceous glands produce sebum.

Skin Functions

• The dermis provides mechanical properties.
• Epidermis provides protective functions.
• The epidermis offers a microbiological barrier via sloughing and protects against chemicals and radiation.
• The epidermis also regulates heat and acts as an electrical barrier.
• The horny layer (SC) has very low permeability to chemicals and contributes to the rate-limiting step in percutaneous absorption
• Stratum Corneum Barrier properties are related to: very high density of cells, its low hydration, the fact that it is composed of keratin and lipids and due to the interstitial region

Routes for Drug Penetration

• Drugs can penetrate via:
  • The continuous stratum corneum
  • Hair follicles with sebaceous glands
  • Sweat Ducts
• Drug penetration across the continuous stratum corneum occurs via intercellular and transcellular routes.

Rational Approach to Topical Formulation

• Main dermatology targets:
  • Skin surface
  • Horny layer
  • Viable epidermis and upper dermis
  • Skin appendages
  • Systemic circulation (Transdermal Route)
• Topical drugs: transepidermal, transappendegeal, or transdermal.

Surface Treatment

• Surface treatment mainly involves cosmetic applications such as:
  • Insect repellants (synthetic like DEET or natural with lemon/eucalyptus oils)
  • Sunscreens (absorb or reflect UV radiation, rated by SPF).

Stratum Corneum Treatment

• Involves:
  • Improving emolliency by raising water content for dry skin.
  • Stimulating sloughing (exfoliation) using agents like salicylic acid or uncooked oats.

Skin Appendages Treatment

• Antiperspirants reduce underarm perspiration by blocking sweat glands.
• Deodorants mask/reduce axillary odor using antimicrobial agents with fragrance.
• Depilatory agents remove hair
• Topical antibiotics and antifungals can also be used.

Viable Epidermis and Dermis treatment

• Treatments address diseases by delivering drugs to receptors effectively.
• Includes anti-inflammatories, anesthetics, antihistamines, antibiotics, and antifungals.

Systemic Treatment

• Transdermal Patches that treat conditions via percutaneous absorption.
• They are used for motion sickness (hyoscine) and angina (nitroglycerin).

Topical vs Transdermal Medications

• Topical and transdermal products are applied to the skin.
• Topical medications act on the surface
• These medications do not reach the bloodstream
• Topical medications act locally, such as hydrocortisone ointment for skin rashes.
• Transdermal medications penetrate the skin and enter the blood, acting systemically, such as nitroglycerin patches for angina.

Semisolid Preparations

• Semisolid dosage forms retain their shape due to plastic behavior.
• They have a permanent 3D structure and specific rheological character.
• Types include: ointments, creams, gels, emulgels, pastes, and poultices (cataplasms).

Semisolid preparation properties

• Ointments: greasy preparations.
• Creams: semisolid emulsions containing medicinal agents in o/w or w/o emulsion.
• Gels: transparent or translucent, non-greasy, aqueous preparations.
• Emulgels: two-phase systems with a gelling agent penetrated by water and emulsified lipids.
• Pastes: contain a higher proportion of finely powdered solid medicament than ointments or gels, with similar bases.
• Poultices (cataplasms): for external use, containing medicaments. The paste is spread on a warm, moist cloth to relieve inflammation and promote healing.

Dosage Form types

• Topical medications come as creams, ointments, liquids, lotions, gels, sprays, foams, powders, and patches.
• Transdermal medications typically come as patches but may also appear in gels or pastes.
• Transdermal vehicles contain penetration enhancers to increase transdermal absorption.
• Not all topical gels are transdermal - Most creams, gels, and ointments are topical.