Rectal and Vaginal DDS

Question 1

Rectal and Vaginal DDS

Answer 1

-Suppositories (“Inserts”)
-Tablets and capsules
-Ointments, creams, Aerosol foams
-Gels and jellies
-Vaginal Sponges and Rings
-Intrauterine devices
-Powders
-Solutions and other liquids

Question 2

Definitions of Suppositories

Answer 2

-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

Question 3

Types of Suppositories

Answer 3

-Rectal: primarily cylindrical
-Vaginal: different shapes (ovoid, cylindrical, globular), bigger than rectal
-Urethra: bigger for males

Question 4

Pros and Cons of the rectal route:

Answer 4

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

Question 5

Therapeutic target and Indications

Answer 5

-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)

Question 6

Release and Delivery of the drug

Answer 6

-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

Question 7

Characteristics of Base and the drug

Answer 7

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

Question 8

What are the Physiologic (Body-related) and Physicochemical (Formulation) factors affecting the Absorption of Suppositories?

Answer 8

-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

Question 9

Types of Bases:
Fatty or Oleaginous Bases

Answer 9

-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:

Question 10

Types of Bases:
Water-Soluble and Water-Miscible Bases

Answer 10

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)

Question 11

Cocoa Butter

Answer 11

-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

Question 12

PEG Bases

Answer 12

-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

Question 13

PEG Bases

Answer 13

-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

Question 14

Glycerinated Gelatin Bases

Answer 14

-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

Question 15

Methods of Compounding Suppositories

Answer 15

▪ 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)

Question 16

Hand Rolling and Shaping

Answer 16

1. 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

Question 17

Fusion method

Answer 17

-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

Question 18

Calibrating molds

Answer 18

1. Fill the molds with melted base (specific gravity known)
2. Cooling and let solidify to suppositories
3. 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

Question 19

When to consider a Drug Displacement of Suppository Base?

Answer 19

-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)

Question 20

Doublr-casting Method

Answer 20

-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

4. remove suppositories, melt and put them again into molds -> cooling and solidify it -> now evenly distributed

Question 21

Problems when compounding

Answer 21

-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

Question 22

Packaging and Labeling

Answer 22

▪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

Question 23

Urethral and vaginal Suppositories

Answer 23

-different dimensions for males and females
-PEG vehicles are mostly used (water-soluble, dissolving)

Question 24

Vaginal Suppositories/Inserts

Answer 24

-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