Lecture 8 - medication via the rectal route Flashcards
describe the rectal anatomy
About 12 cm long
Rectum is part of the large intestine and starts at the sigmoid colon
functions as temporary storage of the faecaes, but usually empty until defection
contain approximately 3ml of rectal fluid
300cm2 surface area
pH of 7.5
what is the important eof rectal drug administration
Rectal drug formulations can be useful for drugs that:
undergo high hepatic first-pass metabolism,
have limited absorption in the upper gastrointestinal tract
are readily degradable or unstable in the gastrointestinal tract
cause irritation to the gastric mucosa
cannot be easily formulated for other routes of administration
have localized actions in the rectum or distal colon
what are factors influencing rectal drug delivery?
physiochemical properties of the drug such as partition coefficient, solubility, degree of ionisation, and particle size
site of drug absorption
retention of the formulation
fluid volume and pH
what formulations are there of rectal administrations
solid dosage forms such as suppositories, capsules and tablets
liquid dosage forms such as enemas
semi-solid dosage forms such as gels, foams and cream
describe solid dosage forms
suppositories are the most common rectally administered dosage form. the drug are other dispersed or dissolved n a suitable base.
key properties for an ideal suppository base are:
should be solid at the storage temperature of the formulation but soften, melt or dissolve in the rectal mucosa
should be non-irritant to the rectal mucosa,
should not chemically interact with the therapeutic agent
should be chemically and physically stable over the period of storage
what are common suppository bases?
lipophilic bases:
cocoa butter
coconut oil
hydrogenated vegetable oils
hard fats
theobroma oil
hydrophilic base;
glycerinated gelatinous
polythene glycols
poloxamers
describe fatty bases
theobrome or cocoa butter traditionally used as a fatty base as it has melting point of 34.5 degrees and is non-irritant
however it shows challenges due to its polymorphism, which means it can exist in different crystalline forms. These forms include:
Alpha crystals with a melting point of 23°C
Beta crystals with a melting point of 34.5°C
Gamma crystals with a melting point of 19°C
The physical form of cocoa butter can change depending on its processing, particularly the degree of heating (up to 36°C) and the rate of the cooling process, which is typically slow
In modern practices, there are natural, semi-synthetic, and fully synthetic fat mixtures available, such as hydrogenated vegetable oils. Some examples provided include trade-named products like Cotmar®, Dehydag®, and Witepsol®. melting points can be titrated eg witepsol range 29-44 degrees
outline the preparation for suppositories
Preparation by melt
Cream melting process
(comparable to tempering chocolate)
lipid base is melted until only a few crystalline seeds are left
The melt can then be cast into suppository moulds, in which it should solidify immediately
The initial crystal seeds will ensure that the base crystallises in the right crystal form.
describe th water soluble and water miscible base, glycerol suppository
The base consists of 14% gelatin and 70% glycerol
gelatine is derived from animal skin and bones by 2 types of hydrolysis;
Type A is produced through acid hydrolysis, resulting in a cationic gelatin.
Type B is produced through alkaline hydrolysis, resulting in an anionic gelatin.
Different types of gelatin have different compatibilities with other substances; for example, Type B gelatin is compatible with zinc oxide.
Glycerol acts to crosslink with gelatin, which enhances the consistency of the suppositories. The base is hygroscopic and is sealed into foil for storage
Because of its water content, the base can be prone to microbial contamination and thus requires preservation
When used for delivering systemic drugs, it is important to minimize the amount of glycerol in the formulation due to its laxative effect.
describe water soluble and water miscible bases specifically peg
PEG varying melting points:
MW 200-600 liquid, 1,000 semi-solids, > 4,000 solid
Only 3ml of liquid/mucus present in rectum, extra water needed sometimes (dip before insertion) otherwise osmotic pain
PEG can develop peroxides during storage air tight packaging
PEG typically melts approx. 50°C
The base disperses in rectal fluid/mucus to release the drug
describe the properties which influence the choice of base for a usppsotitory
drug used in suppositories should be non-irritant, solubility in water and vehicle and amount of drug required for pharmacological response should be considered.
If the drug has low fat solubility and high water solubility, a fatty base is preferred.
If the drug has high fat solubility and low water solubility, an aqueous base is used.
If the drug has low solubility in both fat and water, the choice of base is indeterminate.
The release of the drug from the suppository is a rate-limiting step,Therefore, the formulation should be designed to maximize drug release
decline the release mechanism of a suppository
Melting: Initially, the suppository begins to melt after insertion, likely due to body temperature
Spreading: As the base melts, it spreads and covers a larger surface area, allowing for the drug contained within to come into contact with the mucosal lining of the rectum.
Sedimentation: Concurrently, the heavier particles within the melted base may begin to settle or sediment due to gravity.
Wetting: The particles are then wetted by the rectal mucus, which is a necessary step before the drug can dissolve.
Dissolution: Finally, the drug dissolves in the rectal fluid, which allows it to be absorbed into the rectal mucosa and enter systemic circulation.
what is the calibration method during the process of suppositories being manufactured?
Theobroma Oil BP is used as a standard reference when creating suppository molds, which are typically available in sizes like 1g, 2g, and 4g
The calibration is done volumetrically because the volume-weight relationship can vary depending on the base material used.
To calibrate, a number (for example, 5) of suppositories are formed using only the base material (Theobroma Oil BP in this case).
The average weight per suppository is then calculated. This average weight is important for ensuring that each suppository contains the correct dose of medication.
explain displacement values in suppositories
drugs have different density to the base
The displacement value of a drug is defined as the number of parts by weight of the drug that displaces one part by weight of the base
A specific amount of the drug is required per suppository and the displacement of base is drug dependant
what is the displacement value method calculation and what is is used for?
the displacement value method used for calculating the quantities needed to manufacture suppositories
Weight of base = weight of suppositories−(displacement value
weight of active)
If there is more than one active pharmaceutical ingredient (API), the calculation must be adjusted for each API according to its own displacement value.
