Semi-Solid Dosage Forms: A Comprehensive Review

Semi-Solid Dosage Forms

Learning Outcomes

• Discuss the use and features of dermatologic semi-solid dosage forms.
• Discuss the use and features of ophthalmic and nasal semi-solid dosage forms.
• Discuss the use and features of rectal semi-solid dosage forms.
• Discuss the use and features of vaginal semi-solid dosage forms.
• Discuss emerging technologies in the development of semi-solid dosage forms.

Semi-Solid Dosage Forms Overview

• Gels, creams, ointments, and pastes are semi-solid dosage forms intended for topical application.
• Topical preparations are used for both local and systemic effects.
• Features and uses of topical preparations:
  • Dermatologic
  • Ophthalmic
  • Nasal
  • Rectal
  • Vaginal

Dermatologic Preparations

• In treating skin diseases, the drug in a medicated application should penetrate and be retained in the skin for a period of time.
• Drug penetration into the skin depends on several factors:
  • Physicochemical properties of the medicinal substance
  • Characteristics of the pharmaceutical vehicle
  • Condition of the skin itself
• Differences in emollient and occlusive effects determine the base and product type used.
• Oleaginous bases provide greater occlusion and emollient effects than hydrophilic or water-washable bases.
• Pastes offer even greater occlusion and are more effective than ointments at absorbing serous discharge.
• Creams (usually oil-in-water emulsions) spread more easily than ointments and are easier for the patient to remove.
• Water-soluble bases are non-greasy and are applied and removed easily.

Dermatological Administration

• The patient should clean the area to be treated first.
• A thin layer of medication should be evenly spread on the area.
• The application should not be covered unless specifically needed.
• The pharmacist should ensure the patient understands:
  • Administration method
  • Frequency and duration of use
  • Special warnings
  • Therapeutic goals and outcomes
  • Signs of adverse reaction or allergic response
  • Reasons to discontinue use or seek further guidance

Ophthalmic Ointments and Gels

• Drugs enter the eye through the cornea via diffusion.
• Short residence time on the eye surface is due to rapid tear turnover.
• Ointments and gels provide greater residence time than solutions.
• The base should be non-irritating and soften at body temperature.

Ophthalmic Ointment Requirements

• Must be sterile.
• Sterilization of ointments is more difficult than solutions.
• Must pass the test for metal particles:
  • Microscopic examination of melted ointment.
  • The total number of particles 50 \mu m or larger from ten product tubes should not exceed 50, and no more than one tube should contain eight such particles.
• Must be packaged in collapsible tubes.
• Ointments have a narrow tip.

Ophthalmic Ointment Administration

• Wash and dry hands.
• Apply 0.25 to 0.5 inches of ointment to the inside of the lower lid.
• The patient should face down and slowly close the eye for a few seconds.
• Wipe excess ointment with a tissue.
• Advise the patient that vision will be blurred temporarily.
• Once daily administration is best at bedtime.
• Cap the tube quickly and tightly after each use.
• Emphasize the need to prevent bacterial contamination of ophthalmic products.

Nasal Ointments and Gels

• Drugs introduced into the nasal passage are primarily for localized effects on the mucous membranes and underlying tissues.
• Drug absorption to the general circulation does occur through the rich blood supply feeding the nasal lining.
  • Examples:
    • Analgesic - butorphanol tartrate
    • Hematopoietic – cyanocobalamin (Vitamin B12)
    • Nicotine
• The nasal route holds great promise for the administration of insulin, vaccines, and a number of other polypeptides and proteins.

Rectal Preparations

• Topical use on the perineal area or insertion within the anal canal is to treat local conditions of:
  • Anorectal pruritus (itching)
  • Inflammation
  • Pain and discomfort associated with hemorrhoids
• The drugs employed include:
  • Astringents (e.g., zinc oxide)
  • Protectants and lubricants (e.g., cocoa butter, lanolin)
  • Local anesthetics (e.g., pramoxine HCl)
  • Antipruritics
  • Anti-inflammatory agents (e.g., hydrocortisone)
• Substances applied rectally may be absorbed by diffusion into the general circulation via the network of three hemorrhoidal arteries and accompanying veins in the anal canal.
• The rectal route can be used for the systemic absorption of therapeutic levels of certain drugs (e.g., prochlorperazine) when the oral route is unsatisfactory, as in conditions of vomiting.
• The bases used in rectal ointments and creams include:
  • PEG
  • Emulsion cream bases

Product Application

• External product:
  • Cleanse and dry the area.
  • Spread a thin film over the affected area.
• Internal product:
  • Ointments and creams are packaged with a perforated tip.
  • Clean the tip and screw it onto the tube.
  • Lubricate the tip and insert it into the anus.
  • Squeeze the tube to release the product into the anus.
  • Slowly remove the tip.
  • Remove excess ointment from the perineal area.
  • Clean hands and tip and replace the cap on the tube.

Vaginal Preparations

• Topical products are used to treat:
  • Vulvovaginal infections
  • Vaginitis
  • Conditions of endometrial atrophy
  • For contraception with spermatocidal agents
• External product administration:
  • Squeeze a small amount of product onto fingers or area.
  • Spread over the affected area.

Internal Product Administration

• The product is administered to the vagina using an applicator.
• The applicator may be prefilled or filled by the patient.
• Fill by screwing the applicator onto the tube and squeezing the tube until the plunger reaches the marked stopping point.
• Instruct the patient to lie down on her back and insert the applicator as far as possible without discomfort.
• Depress the plunger until it stops and withdraw the applicator carefully.

Vaginal Foam Administration

• Vaginal foams are packaged in aerosol canisters.
• Oil in water emulsions resembling light creams.
• Administer similarly to ointments.
• Fill the inserter device with the canister.
• Place the filled inserter in the vagina and depress the plunger.
• Wash hands thoroughly after use.

Vaginal Product Administration - Additional Notes

• Once daily administration is best at bedtime:
  • Medication retention
  • Avoid leakage
  • Less soiling of clothing
• Creams are preferred over ointments.
• Pregnant patients must not use without physician approval.
• Tampons must not be used during intravaginal treatment.
• Keep tightly closed when not in use.

Emerging Technologies

Muco/bio-adhesiveness:

• Bio-adhesive polymers as a whole and muco-adhesive polymers in particular have been used to improve residence time and provide sustained drug delivery.

Controlling Drug Release

• Excipients (e.g., surfactant, gelling agent, self-emulsifying agent) increase drug release or enable sustained drug release.

Enhancing Drug Absorption:

• Absorption enhancers disrupt the skin or mucosal membrane to increase drug bioavailability.

Improved Stability at High Temperature

• Formulations are able to withstand tropical climates by the use of a water-soluble base (e.g., high molecular PEGs).

In-situ Gel System

• Products are in sol form in the container, i.e., before application, but change to gel forms under various physiological conditions.
• The gelation or sol-gel transition is triggered by one or a combination of different stimuli (pH, ions, etc.).
• Improves contact time and drug retention.
• Ease of application and manufacturing due to their minimum viscosity.
• Reduced frequency of administration

Thermo Gel Systems:

• Novel polymers with thermo-sensitive and muco-adhesive properties.
• Sol-gel transition temperature can be adjusted around 37^\circ C.
• Liquid at ambient temperature, which facilitates preparation and eases spreading in the rectal cavity.
• Gels at body temperature.
• Muco-adhesive properties help maintain the gel for a prolonged period of time.