Suppositories and Inserts- Dr. Miroshynk

Based off Dr.Miroshynk’s “Final Exam Study Guide”

• Suppositories and inserts: definition and clinical use.

  • Suppositories

    • the term used for the solid dosage forms only designed for rectal administration

    • solid dosage forms in which one or more APIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into the rectal area to provide local or systemic effect

    • Uses: promote defecation, treat anorectal diseases, introduce drug into the body

  • Inserts- the similar dosage forms that are inserted into a naturally (nonsurgical) occurring body cavity other than the mouth or rectum

    • Are solid, single-dose dosage forms in which one or more APIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into the vagina

    • Uses: vaginal infections, vaginal disorders

• The advantages and disadvantages of rectal/vaginal drug delivery versus oral drug delivery.

  • Disadvantages of rectal

    • rectal has lower rate and extent of drug absorption compared to oral

    • poor patient compliance

    • upward movement of the dosage form can increase 1^st pass metabolism

    • suppositories can leak

    • insertion can be hard

    • erratic absorption

  • Advantages of rectal

    • Ideal for drugs liable to degradation in the GI

    • Hepatic 1^st-pass elimination of high clearance drugs is partially avoided

    • Better for drugs that irritate the stomach

    • Large doses can be administered

    • Taste/smell masking

  • Benefits of Vaginal

    • Local drug delivery

    • If Oral intake restricted

    • Preferential delivery to the uterus

    • Favorable alternative to the parental administration

    • Avoids hepatic 1^st pass effect

    • Enables self-administration and removal

  • Limitations of Vaginal Administration

    • Gender specific

    • Premature discharge/leakage of the dosage form

    • Systemic absorption

• Physiological and physicochemical factors affecting the drug absorption from suppositories and vaginal inserts.

  • Physiological- Rectal

    • Quantity of fluid available

    • Property of rectal mucus

    • Contents of the rectum

    • Motility of the rectal wall

    • Lymphatic circulation

  • Physiological- Vaginal

    • Epithelium thickness

    • pH

    • amount, composition, and viscosity of the vaginal fluids

  • Physicochemical of APIs- Rectal

    • Surface properties

    • Log P

    • pKa

    • Particle size

    • Amount

  • Physiochemical of APIs- Vagina

    • MW

    • Log P

    • pKa

    • particle size

    • surface charge

  • Physicochemical of the base- Rectal and Vaginal

    • Composition

    • Melting behavior

    • Rheological properties

• Suppository/inserts bases: classification and properties.

  • Properties:

    • Solid at room temp

    • Non-irritating

    • Nontoxic

    • Physiologically inert

    • Stable

    • Compatible w/ other drugs

    • Viscous enough to prevent fluid leakage

  • Classification

    • Fatty

    • Aqueous

      • Less frequently used, m.o. above body temp, DOES NOT MELT at body temp, but slowly dissolves in body fluids

      • Ex: PEG bases

        • Must be at least 20% water

        • Issues: hygroscopicity, slow down drug release, oxidation

      • Ex: Glycerinated Gelatin Base

        • Translucent, hygroscopic

        • Not for rectal use- only vaginal

        • Issues: hygroscopicity, hard to manufacture, potential API issues

      • Water soluble

      • Water miscible

    • Water-dispersible

• Polymorphism of cocoa butter.

  • Can crystallize into many different forms

  • Various melting points

  • Exhibits polymorphism due to triglyceride content

• Principles of drug incorporation into suppository bases.

  • base-soluble drugs

    • menthol

    • dissolve in molten base

  • water-soluble

    • Novacain, ZnSO4

    • Use concentrated aqueous solutions

    • Filtrate before mixing with the base

  • insoluble drugs

    • zinc oxide, bismuth subgallate, iodoform

    • spatulate powder with molten base

• Typical suppository excipients.

  • M.p. increasing agents

    • Beeswax

    • Magnesium stearate

    • Colloidal silicon dioxide

  • M.p. decreasing agents

    • PEG

    • Polysorbate 80

  • Visocity-increasing agents

    • Silica gel

    • Tend to decrease release rate

  • Preservatives

  • Antioxidants

  • Surfactants

    • Absorb many drugs

    • Only for lipophilic bases/drugs

• The methods of suppository preparation.

  • Fusion molding

    • Most common

  • Compression

• ‘The principle of opposite characteristics’ as applied to suppositories and inserts.

  • We want mismatched drug and base

  • Ex: oil-soluble drug and water-miscible base

  • 

• Packaging and storage.

  • Packaging

    • Tightly closed glass containers

    • Compartmented boxes

    • Individually wrapped

    • Disposable molds

  • Storage

    • Humidity most important/ keep low

    • Best to keep refrigerated

• Quality control of suppositories.

  • Texture uniformity

  • Disintegration

  • Dissolution rate

  • Content uniformity

• Key patient counseling information associated with suppositories and inserts.

  • Warm to room temp if it was in the fridge

  • Cocoa butter-based sup should be rubbed gently

  • Glycerinated gelatin or PEG sups should be moistened w/ water before insertion