Rectal and Vaginal DF Flashcards
What are suppositories?
- used inside rectum
- melt, soften, or dissolve at body temperature
- semi solid or solid dosage forms intended to be inserted into body orifices
Vaginal - inserts or pessaries
Urethra - inserts or bougies
What are the advantages?
- People who cannot swallow
- Treats lower parts of GI tract diseases
- GI tract irritant drugs
- Once daily use
- Local and systemic effect
- Avoids first pass metabolism if administered correctly
What are the disadvantages?
- Poor compliance
- Variation of absorption
- Discomfort and leakage
- Irritation of mucous membranes
- Upward movement of suppository from local site can increase first pass metabolism
What is the shape of rectal suppositories? Weight? Local action? Systemic action? How much does the drug content vary?
- Bullet and Torpedo shape
- 1 g (child), 2g (adult), 4-5 g (rectal rocket)
- Local action: Hemorrhoids, Infection, Itching
- Systemic action: Antinauseants, analgesics, hormones
- Content varies from 0.1 to 30-40%
Shape of vaginal inserts? Weight? Bases? Uses?
- Globular, oval or cone shaped
- 3 to 5 g
- Bases are water soluble or water miscible (polyethylene glycol or glycerinated gelatin)
Uses:
Contraceptives (Nonoxynol-9, spermacide)
Vaginal hygiene (antiseptics)
Gyno ailments (vaginal infections, hormone deficiency)
Shape of urethral inserts? Size? Weight? Uses?
- Cylindrical
- 3-6 mm in diameter, 50 mm in length for females, 125 mm for males
- 2 g (females), 4 g (males)
Uses:
- Erectile dysfunction
- Local anesthetic for urethral examination
- Antibacterial
What are the active ingredient examples?
Local action
Antifungal: Clotrimazole Astringent: Bismuth Subgallate Anti-inflammation: Hydrocortisone Hemorrhoids: Zinc sulfate Anesthetics and antiseptics
Systemic action
Antiemetic: Prochlorperazine, Dimenhydrinate
Analgesic: Diclofenac, Acetaminophen, Aspirin, Morphine
What are the additives?
Preservatives: Parabens Antioxidants: Butylated Hydroxytoluene Plasticizers: Propylene glycol, Cetyl alcohol Solubilizing agents: Surfactants Absorption enhancers: Surfactants Viscosity enhancers: Silicon dioxide
What should ideal suppository bases look like?
- Melt at body temp or dissolve in rectal fluids
- Stable if heated above mp
- Non toxic or non irritant to membrane
- Release drug easily
- Stable on storage
- Non-absorbable
- Be compatible with drugs
- Keep its shape when handled
What are the fatty/oleaginous/hydrophobic bases?
- Cocoa butter
2. Synthetic/semi synthetic fatty bases (Witepsol, Fattibase)
What are the hydrophilic/water soluble/ water miscible bases?
- Glycerinated gelatin
2. Polyethylene glycols (PEG)
What is cocoa butter?
- Yellowish white solid with a chocolate like odour
- Mixture of triglyceryl esters of palmitic, oleic, stearic and other fatty acids
- Softens at 30 and melts at 34-35 (B form)
What are the advantages of cocoa butter?
- Melts readily on warming, sets rapidly on cooling
- Compatible with many ingredients
- Non irritating
What are the disadvantages of cocoa butter?
- Polymorphism when heated above its MP
- Adherance to mold
- Should be refrigerated
- Slow deterioration during storage
- Poor water absorbing capacity
- Leakage from body
What are semi synthetic fatty bases?
hydrolyzing vegetable oil + hydrogenation + re-esterifying the acids with glycerol
Fattibase:
- mixture of palm, palm kernel and coconut oil, self emulsifying glyceryl monostearate, polyoxyl stearate
- mp: 35.5 to 37 degrees
Witepsol:
- Triglycerides : Saturated fatty acids (C12 and C18 range)
- Mp range of 33-35 degrees
What are the advantages and disadvantages?
Advantages:
- Better contraction
- No polymorphism
- Rapid solidification
- Tolerance to oxidation
- Improved drug release and bioavailability (with surfactants)
Disadvantages
- Some bases need to be stored in refrigerator
- Becomes brittle if cooled too quickly (witepsol)
- May have dehydrating effect
What are glycerinated gelatin bases?
- 10% water + 70% glycerin + 20% gelatin
- Slowly dissolves in the secretions of the mucous lining of the rectum and vagina
- Used frequently for vaginal suppositories
- Better for antiseptics than fatty bases - dissolves slowly ~30 to 40 min
- Used less often than fatty bases because of disadvantages
What are the disadvantages of glycerinated gelatin base?
- Have a physiological action (osmotic laxative effect)
- Hygroscopic
- Irritation and dehydration in mucosa
- Difficult to prepare and handle
- Dissolution depends on age of the base and quality of the gelatin
- Not compatible with protein precipitants like acids and other agents
Type A gelatin = cationic antiseptic
Type B = anionic antiseptic
What are polyethylene glycols or macrogols?
- Mixtures of PEG of various molecular weights
- Physical properties adjusted by varying weight
- Gradually dissolve and disperse in fluids
- Prolonged release of the drug (30 to 50 min to dissolve)
- Polybase: Mixture of PEGs and polysorbate 80
Advantages of PEGs?
- Easier to prepare
- Do not stick to the mold
- Contract significantly on cooling
- No cool storage required
- Do not leak from the body
- Absorb water well
- Have good solvent properties
- Reliable release of drugs
Disadvantages of PEGs?
- Hygroscopic: mucosa irritation
- Should be moistened with water before insertion
- Contracts significantly on cooling (forms pits and holes)
- Incompatible with phenolic substances (tannic acid, aspirin, benzocaine, salicylic acid)
What are the rectal cavity physiological factors?
- Small mucus volume (1-3 mL)
- Low buffer capacity (pH 6.8-7.4)
- Presence of fecal matter
- Small SA
How is blood supplied to the rectal area?
- Inferior rectal vein carries blood to the inferior venacava and bypasses liver
- Superior rectal vein carries blood to the superior part of the rectal cavity to the liver
What are the formulation and drug properties factors?
Melting or dissolution of base
- Aqueous solubility and dissolution
- Melting of base
Release and diffusion of drug
- Solubility of drug in vehicle and rectal fluids
- Drug particle size
- Spreading capacity
- Viscosity of base at rectal temp
Rectal mucosa
- Pka of drug
- Buffer capacity
- Ph induced in rectal fluids
- Partitition coefficient of drug
