Polymorphism in Pharmaceuticals

Pharmaceutics 3 - 2020

• Course taught by Dr. Noha Younis
• Focuses on ointments, types, classification, and characteristics of an ideal ointment

Chapter One - Ointments

• Definition: A homogeneous, viscous semisolid preparation, commonly greasy and oily (Oil-80%, Water-20%). Intended for external application to skin or mucous membranes. Used as emollients, protective, therapeutic or prophylactic agents.

• Types of Ointment:

  • Medicated ointment: Contains an active pharmaceutical ingredient (API) for protective, therapeutic or prophylactic purposes.
  • Non-medicated ointment: Used for physical effects like protection (barrier), emollients or lubricants.

• Classification of ointments according to place of action:

  • Epidermic: Acts on the epidermis (outer skin layer).
  • Endodermic: Acts on deeper layers of cutaneous tissues (penetrates into skin).
  • Diadermic: Penetrates deep to release medicaments into body fluids, like systemic circulation.

• Characteristics of an ideal ointment:

  • Physically and chemically stable.
  • Finely divided active ingredients uniformly distributed, smooth and free from grittiness.
  • Inert, odorless base.
  • Low irritation and sensitization index.
  • Should not retard wound healing.
  • Should melt at body temperature for efficient medicament release.
  • Compatible with common medicaments and skin.
  • Easily washable with water.
  • Economical and easy to transport.

• Advantages of ointments:

  • Site-specific action with fewer side effects.
  • Avoids first-pass metabolism.
  • Convenient for unconscious patients.
  • Chemically more stable and easier to handle compared to liquid dosage forms.
  • Suitable dosage forms for bitter-tasting drugs.

• Disadvantages of ointments:

  • Staining and cosmetically less aesthetic.
  • Application with fingertip may contaminate the formulation or cause irritation.
  • Bulkier to handle compared to solid dosage forms.
  • Dose accuracy is determined by the quantity applied.
  • Physio-chemically less stable than solid dosage forms.

Types of Ointment Bases

• Oleaginous ointment base (hydrocarbon base, water in oil):
  • A choice of base for dry, chapped skin.
  • Examples:
    • Petrolatum (Soft paraffin):
      • Pale yellow, odorless; melting point 38-56°C (yellow)
      • White, odorless, melting point 38-56°C (white) -Suitable for epidermal preparations.
    • Hard paraffin: Solid from hydrocarbon obtained from petroleum; colorless or white, odorless mass. Used to harden or stiffen ointments.
• Absorption ointment bases (water in oil):
  • Hydrophilic/absorbent
  • Examples: -Anhydrous lanolin (wool fat): Non-soluble in water but absorbs a large amount of water
• Water removable (water washable base):/water soluble base:
  • Emulsifying bases (oil in water).
  • Examples: Polyethylene glycol polymers (PEG) - water soluble, non-volatile, inert, not hydrolysis, not support the bacterial growth or mold growth.
• Other bases:
  • Animal fats and plant fats (spermaceti, carnauba wax)

Methods of Preparation of Ointment

• Incorporation (trituration):
  • Used for insoluble substances.
  • Levigate insoluble substance with base until smooth.
  • Incorporate into remainder of the base.
  • Water-soluble salts may be dissolved in small quantities of water and then incorporated into base.
  • Fusion may be used if high melting point ingredient will be incorporated in a molten base then all the other ingredients added, mixed and stirred to have uniformity
• Fusion: Ingredients melted together in descending order of their melting points to ensure homogeneity.

Evaluation Parameters of Ointments

• Physical methods: Rate of absorption, non-irritancy, rate of penetration, rate of drug release, rheological properties, content uniformity
• Microbiological methods: Test of microbial content, test of preservative efficacy.

Ophthalmic Ointments

• Sterile, homogeneous, semi-solid preparations for eye application.
• Prepared from non-aqueous bases (e.g. soft paraffin, liquid paraffin, wool fat).
• May contain additives like antimicrobial agents, antioxidants, and stabilizing agents.
• Materials must be impalpable to prevent eye discomfort.
• Advantages: Longer contact time, flexibility in drug choice, improved drug stability and storage stability.
• Disadvantages: Sticking of eyelids, blurred vision, poor patient compliance, interfere with corneal epithelial cell attachment, matting of eyelids.

Creams

• Semisolid dosage form containing one or more drug substances dissolved or dispersed in a suitable base.
  • Lighter than ointments
• Formulated for application to skin or mucous membranes, especially when occlusive effect is not necessary.
• Two main types: Oil-in-water (O/W) and water-in-oil (W/O).
• O/W creams: Water washable, causes rapid absorption and penetration, thin, white, smooth consistency, cosmetically acceptable, and easily washed off with water..
• W/O creams: Creamy, white or translucent; more difficult to handle, but drugs are more readily released from W/O than O/W.
• Properties of creams: rapid absorption and penetration, thin, white, smooth consistency, more comfortable and cosmetically acceptable. More easily washed off usage.

Pastes

• Semisolid preparations with high percentage of insoluble particulate solids (often > 50%).
• Thicker and stiffer than ointments.
• Used as protective barriers, absorb and neutralize harmful chemicals and protect skin lesions.
• Examples of insoluble ingredients include starch, zinc oxide and calcium carbonate.

Liniments

• Alcoholic or oleaginous solutions or emulsions of medicinal substances.
• Used for rubefacient and counterirritant effects.
• Oily liniments often function as protective coatings.
• Applied with rubbing to affected area.

Colloidions

• Liquid preparations containing pyroxylin (nitrocellulose) in a mixture of ethyl ether and ethanol.
• Applied with a soft brush to form a thin film of pyroxylin.
• Used for external application.

Glycerites

• Solutions or mixtures of medicinal substances in 50% or higher concentration of glycerin.
• Useful as pharmaceutical solvents and for concentrated solutions.
• Hygroscopic, stored in tightly closed containers.
• Used for topical administration.

Suppositories

• Semisolid or solid dosage form intended to be inserted into body cavities (rectum, urethra, vagina).
• Melt or soften at body temperature to release the drug.
• All types of suppositories melt at normal body temperature after introducing in body cavity and produce their effect.
• Advantages: alternated route of administration; suitable for unconscious patients; suitable for drugs with bad odor and taste.
• Types: Rectal, urethral, vaginal, nasal, or ear cones; different shapes and sizes according to body cavity for insertion.
• Ideal properties: solid form at room temperature, not irritate, stable in storage, no change in appearance, colour, or odour., retain hardness, and shape when handled, not stick to mould, melt at body temperature, release drug rapidly, do not react with drugs or additives.
• Base types: hydrophilic (glycero-gelatin) and lipophilic (cocoa butter).
  • Hydrophilic bases are better suited for mixtures of water and other materials.
  • Lipophilic bases are better suited for mixtures of oils.

Powders

• Fine state of division of solid drugs, for internal or external use. -Advantages: good chemical stability, useful for bulky drugs, easy to swallow, rapid dissolution in fluids, less incompatibility, easier to carry. -Disadvantages: not suitable for drugs unstable in atmospheric conditions, bitter or irritating drugs, inaccurate doses in bulk powders. -Types: divided powders (packets), bulk powders (cardboard, glass, or plastic containers-usually non-potent drugs), dusting powders (superficial application to skin), insufflations (inhalation into cavities), snuffs (inhalation into nasal passages), dentifrices (tooth powders).
• Challenges include hygroscopic or deliquescent powders, effervescent problems, incorporation of liquids or extracts and explosive mixtures
• Preparation Methods: Wet granulation, dry granulation, direct compression, methods of granulation.

Capsules

• Solid dosage forms containing one or more drugs enclosed in a gelatin shell, for internal use.

Tablets

• Solid dosage forms prepared usually by compression of powdered drug and excipients.
• Advantages: compact, easy to swallow, better patient compliance, lower cost, no need for measuring precise doses.
• Disadvantages: poor dissolution profile, difficult for children/elderly to swallow, stability problems in some drugs.

Test your knowledge on polymorphism and crystallization processes in pharmaceuticals. This quiz covers various aspects including factors affecting polymorphism, methods of supersaturation, and best practices in formulation. Perfect for students and professionals in the field of pharmacy and materials science.