Rectal and Vaginal DDS Flashcards
Rectal and Vaginal DDS
-Suppositories (“Inserts”)
-Tablets and capsules
-Ointments, creams, Aerosol foams
-Gels and jellies
-Vaginal Sponges and Rings
-Intrauterine devices
-Powders
-Solutions and other liquids
Definitions of Suppositories
-Solid DDS with the drug incorporated in a base
-administration via any of several body orifices ->
rectum, vagina, or urethra
-they work by melting at body temperature or dissolving in body fluids and releasing the drug over time
Types of Suppositories
-Rectal: primarily cylindrical
-Vaginal: different shapes (ovoid, cylindrical, globular), bigger than rectal
-Urethra: bigger for males
Pros and Cons of the rectal route:
PROS
-Avoids GI tract: no degradation by acids and enzymes; the lower third of the rectum bypass first-pass metabolism
-Administration of large doses
-simple and painless
-can dose unconscious patients or those who can’t take it orally
-fast acting
-can be divided
CONS
Upward movement
-patients don’t like it
-Leakage and insertion can be problematic
-Expulsion potential
-slow absorption
Therapeutic target and Indications
-Local: Constipation, hemorrhoid relief, itching, inflammation
-Systemically: has a lot of blood supply (but it has been variation for systemic absorption in different patients -> erratic)
Release and Delivery of the drug
-made of polymers and bases that melt at body temperature
-Dissolving in aqueous secretions of the mucous membranes (drug partition out of the base) -> get absorbed and shows its effect
Characteristics of Base and the drug
To get released, a water-soluble base needs a non-water-soluble drug -> so that it separates from the base f.e. Cocobutter is oily, a water-soluble drug is used for an easier separation
What are the Physiologic (Body-related) and Physicochemical (Formulation) factors affecting the Absorption of Suppositories?
-Physiologic:
▪Colonic Content: should be empty
▪ Circulation Route: varies in patients
▪ pH (7-8) and Lack of buffering of rectal fluids
-Physicochemical:
▪ Lipid-Water Solubility: incorporate water-soluble drugs in lipophilic bases (Coconut butter) and lipophilic drugs in water-soluble bases (Polyethylene glycol, PEG); water-soluble bases will not melt, they will dissolve (so water-soluble drugs can also be used) -> choose by log P
▪ Particle Size -> drug is dispersed (suspension, emulsion) -> smaller the size, greater the surface area, and faster the dissolution and absorption
▪ Nature of the Base
Types of Bases:
Fatty or Oleaginous Bases
-Fatty or Oleaginous Bases: work by melting and releasing the drug -> f.e. Cocoa butter (theobroma oil) (Cocoa butter has different polymorphic states, careful with heating
-> use substitutes: Synthetic triglycerides that are not polymorphs (e.g. Fattibase and Wecobee)
-Water-Soluble and Water-Miscible Bases:
Types of Bases:
Water-Soluble and Water-Miscible Bases
For lipid-soluble drugs (also for water-soluble bc they dissolve at body temperature), work by dissolving and releasing the drug
-Polyethylene glycols (PEGs), Glycerinated Gelatin, Hydrophilic Bases (Emulsion, Hydrogels)
Cocoa Butter
-often for constipation or hemorrhoids soothing effect when applied
-Variety of crystal structures (polymorph) – when heated too much it can form a polymorph that will not melt at body temperature
-Desired form: Beta form 31-34° C -> formed by gradual heating in water bath
Gamma form 18° C
Alpha form 22° C
Beta prime form 27° C
PEG Bases
-for lipid-soluble drugs
-melt (not at body temperature) and dissolve the drug pretty quickly
-the MP is not as high as for Cocoa butter
-no issues with polymorph forms
-liquid PEGS: 200-600 - solid: 900- 8000 (higher MW)
-as the MW increases water solubility decreases, and viscosity increases
-very stable
PEG Bases
-for lipid-soluble drugs
-melt (not at body temperature) and dissolve the drug pretty quickly
-the MP is not as high as for Cocoa butter
-no issues with polymorph forms
-liquid PEGS: 200-600 - solid: 900- 8000 (higher MW)
-as the MW increases water solubility decreases and viscosity increases
-very stable
Glycerinated Gelatin Bases
-common forumla: 70p Glycerin + 20p Gelatin + 10p water
-no color or flavor needed
-Gelatin type to use: Edible, Type A or Type B
-Good for use as a vaginal suppository/insert base
Methods of Compounding Suppositories
▪ Preparation by Compression (Manufacturer method)
▪ Preparation by Hand Rolling and Shaping
▪ Preparation by Fusion (melting the base, adding the drug, and solidifying it)
▪ Double Casting method (don’t need to clarify the mold, most accurate method)
Hand Rolling and Shaping
- Weigh ingredients 2. chop cocoa butter and mix together 3. Apply gentle heat 4. Shape and form
-practice and skills needed
-tend to crack or hollow in the center, if the mass is not softened
Fusion method
-Most commonly used, base and drug are fused
1. Lubricate and calibrate the mold
2. Melt the base (dry or water bath)
3. Add the drug and wait until it is dispersed or dissolved
4. Mix and pour into molds
5. Cooling and solidify
-Calibrating molds: Calculation of volume and amount of drugs
Calibrating molds
- Fill the molds with melted base (specific gravity known)
- Cooling and let solidify to suppositories
- measure the weight -> calculate the volume of each mold (subtraction of active drug to get the amount of base needed)
(the amount on the prescription is for 1 single suppository)
-if the amount is significantly present in the suppository (2% or greater) a 1:1 subtraction is not possible -> take the displacement value of the base into account
When to consider a Drug Displacement of Suppository Base?
-Drug intended for systemic effect - the mass of dose is important
-if the amount is significantly present in the suppository (2% or greater
- Density difference between the base and the drug
(often the case with cocoa butter)
Doublr-casting Method
-takes longer, but is more accurate, no calculation is needed
1. prepare excess base (50-60%) and take 1/3 of it
2. add the dissolved drug, mix it, and half-fill the molds
3. fill the molds with base -> cooling and solidify, now the drug is concentrated on the bottom and not equally distributed
- remove suppositories, melt and put them again into molds -> cooling and solidify it -> now evenly distributed
Problems when compounding
-Vegetable extracts: hard to disperse uniformly, so use LEVIGATION
-crystalline materials: each has its own melting point ->crystalline with the highest melting point is melted first
-Liquid ingredients have to be added with powder so that the liquid can be absorbed and the suppository can keep its solid form
-Excess powder: LEVIGATE with glycerin (liquify it) before adding it to the suppository
Packaging and Labeling
▪Ointment Jars or Suppository Boxes
▪Wrap in foil for handling and identification
Council: Remove foil, Unwrap, moisten, and insert, don’t remove it once it is inserted
Store in Refrigerator for cocoa butter, not needed for PEG -> never freeze bc it can contract, expand and fracture
Urethral and vaginal Suppositories
-different dimensions for males and females
-PEG vehicles are mostly used (water-soluble, dissolving)
Vaginal Suppositories/Inserts
-Also called pessaries or Inserts
-Generally “tablets”
-Water-soluble bases (PEGs or Glycerin) most convenient, Oleaginous bases tend to “leak”
-Contraceptive, hormones, hygiene purposes, infections -> locally
-also systemically (Highly vascular area): for peptides and other therapeutic agents (few proteases are present
