Pharmaceutical Science: Suppository Formulation

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Questions and Answers

What is the typical size and shape of a suppository?

Around 25 mm, triangular-shaped

About 20 mm, square-shaped

Roughly 40 mm, flat and disc-shaped

Approximately 32 mm, cylindrical with tapered ends (correct)

What is a common characteristic of the drug content in suppositories?

It is generally fixed at 20%

It can span from 0.1% to 40% (correct)

It typically varies from 10% to 30%

It ranges from 0.5% to 50%

Which of the following is NOT listed as a type of vaginal preparation?

Vaginal tablets

Vaginal foams

Vaginal gels (correct)

Vaginal sprays

What is a primary consideration in the design of suppositories?

Ease of insertion Signup and view all the answers

Which ingredient commonly irritates when used in the formulation of suppositories?

PEG Signup and view all the answers

What is a significant characteristic of suppository bases used for drug formulation?

Must melt, soften, or dissolve at body temperature Signup and view all the answers

Which of the following is a common fatty base used in suppository formulation?

Cocoa butter Signup and view all the answers

What is a potential issue that may arise from the dissolution of drugs in suppositories?

Osmotic absorption causing pain or unpleasant sensation Signup and view all the answers

What is the primary reason for using a mixture of bases in suppository formulation?

To control the hardness and melting temperature profiles Signup and view all the answers

What characteristic must a suppository base exhibit regarding temperature changes?

Exhibit enough volume contraction during solidification to permit removal from mould Signup and view all the answers

What is the melting range of cocoa butter?

30-36°C Signup and view all the answers

Which characteristic of cocoa butter contributes to its difficulty in solidifying?

Marked polymorphism Signup and view all the answers

Which of the following bases is derived from coconut oil?

Weecobee bases Signup and view all the answers

What is a potential issue when using synthetic fatty bases?

Brittleness due to rapid cooling Signup and view all the answers

What does the presence of β crystals in cocoa butter imply?

Metastability with potential changes Signup and view all the answers

Which property of synthetic fatty bases helps in achieving non-uniform distribution of drug particles?

Low viscosity when melted Signup and view all the answers

Which two bases are classified as water-soluble and water-miscible?

Glycerinated gelatin and macrogols Signup and view all the answers

What is the key factor in the solidifying process of synthetic fatty bases?

Quick cooling is required Signup and view all the answers

What is the primary characteristic of PEG suppositories in terms of their behavior at body temperature?

They dissolve slowly in bodily fluids instead of melting. Signup and view all the answers

Which of the following melting temperature ranges correctly corresponds to PEG with a molecular weight of 600?

20-25 °C Signup and view all the answers

What effect does the hygroscopic nature of PEG have on its handling and usage?

It leads to a dehydrating effect and can irritate tissues. Signup and view all the answers

What is the significance of the displacement value (DV) in the context of suppository bases?

It indicates the number of parts by weight of active ingredient that displaces the suppository base. Signup and view all the answers

Which of the following is true regarding the combination of different PEGs?

They can be combined through fusion regardless of their physical states. Signup and view all the answers

What potential issue can arise from adding preservatives to PEG formulations?

Problems of incompatibility with the formulation. Signup and view all the answers

What should be done to PEG suppositories that do not contain at least 20% water?

They should be moistened prior to use. Signup and view all the answers

Study Notes

Compounding of Suppositories & Pessaries

The rectum is the straight section of the GI tract, extending from the last 150-200 mm of the colon.
It has a hollow structure with a smooth, flat inner surface.
Three rectal valves are present inside.
The anus separates the rectum from the external environment.

Rectal Subdivision

The rectum is divided into two main parts: the anal canal (taking up 20%) and the ampulla (making up 80%).
The rectal wall has a single layer of epithelial cells, with cylindrical and goblet cells, including mucus.
The total surface area of the rectal mucosa is approximately 300 cm², and its volume is roughly 3 mL.
The pH of the rectum is 7.5, and its buffer capacity is minimal.

Rectal Anatomy

The rectum is illustrated with sections of anal columns, the pectinate line, external and internal anal sphincters, and the anal canal.

Rectal Drug Delivery Advantages

Delivering drugs rectally offers both localized and systemic effects.
Drug absorption occurs primarily through passive diffusion.
Sterase and peptidase enzymes are absent in the rectal tract.
Beneficial for patients who can't take oral medications (due to vomiting, unconsciousness, or other factors) or for drugs that are sensitive to stomach acid, enzymes, or the first-pass effect in the liver.
Useful for drugs with a bad taste.

Rectal Drug Delivery Disadvantages

Patients often have a strong aversion to rectal administration.
Absorption is slow and incomplete in the rectal region.
Poorly absorbed low-solubility drugs are ill-suited for this method.
Variability occurs in absorption responses between individuals.
Proctitis (inflammation of the rectum) is a potential complication.
Production and storage of suppositories can pose challenges due to temperature sensitivity and other issues.

Vaginal Anatomy

The vagina is a 10 cm fibromuscular tube with an approximate surface area of 60 cm².
The vagina has three distinct layers: the adventitia, mucosa, and muscularis.
The presence of rugae and micro-ridges on the epithelial surface increases surface area.
A substantial network of blood vessels in the vaginal wall enables both local and systemic drug absorption.

Vaginal pH

The pH of the vagina is maintained at a level of 3.5-4.5 by the bioconversion of lactic acid produced by vaginal microflora.
Vaginal fluids result from secretions from various glands.
Peptidase enzymes are present in the vagina and will degrade protein and amino acids but have lower activity compared to the GI tract.
Vaginal wall thickness, fluid volume and pH are influenced by age, cyclical changes and pregnancy for example a 50-year-old woman may have a less thick vaginal wall.

Intravaginal Delivery Advantages

The vagina's structure retains drug forms, making drug release prolonged.
Systemic side effects are minimized.
High bioavailability.
Avoidance of first-pass metabolism by the liver.
Quicker drug onset of action.
Self-medication is possible.

Intravaginal Delivery Disadvantages

This delivery method is gender specific.
Cultural and traditional aversion may lead to non-compliance from individuals receiving treatment.
A limited selection of drugs is available for this method.
Variability in drug absorption among individuals.
Personal hygiene is a concern.
Some drugs are sensitive to vaginal pH.
Sexual activity can impact dosage.

Rectal Preparations

Rectal medications are intended for absorption with optional systemic or topical effect, which can include diagnoses.
Common types of rectal preparations include suppositories, rectal capsules, solutions, suspensions, powders, tablets, semi-solid preparations (like ointments), enemas, foams, and tampons.

Vaginal Preparations

Also used for local and systemic effects.
Dosage forms like pessaries, suppositories, vaginal tablets, capsules, solutions, sprays, ointments, and foams are possible.

Suppository Description

Typically 32 mm (1.5 inches) long, cylindrical with an optional tapered end, bullet, or torpedo shape for easier insertion.
Weights vary.

Suppository Drug Types

Local use as in hemorrhoid treatment, laxatives, or anal pain relief.
Systemic use for pain relief (e.g. analgesia, like oxymorphone HCl) or nausea and vomiting medication.
Drug content can vary between 0.1% and 40%.

Suppository Base Characteristics & Release

Suppository bases must melt, soften, or dissolve at body temperature to release their medication.
The base type affects release; dissolving in the rectum, melting on the mucus layer, or other actions.
Dissolution rate is limited by rectal fluid amounts.
Dissolved drugs enter the mucosal layer while suspended drugs go through the rectal motility or gravity before dissolving.

Suppository Base Types

Fatty or oleaginous bases are common options, like cocoa butter (classic), hydrogenated fatty acids from vegetable oils, and mixtures to achieve the desired texture and temperature properties.
Cocoa butter is a fatty base made from Theobroma cacao seed that has a yellowish-white solid consistency.
A triglyceride of various fatty acids (e.g., oleopamito-stearin and olea-distearin) makes it's melting range 30-36°C.
It is often combined with other substances to modify its properties.
Other options include synthetic/semi-synthetic bases produced by hydrogenation of vegetable oils and various mixtures with varying textures and properties. These include ADEPS SOLIDUS, FATBASE, and mixtures from palm, coconut, and/or other oils with self-emulsifying agents. Another option comprises white petrolatum with polyethylene glycol (PEG).

Water-Soluble/Water-Miscible Bases

Glycerinated gelatin and polyethylene glycols (PEGs) are water-soluble/water-miscible bases.
Glycerinated gelatin (GG) involves mixing granular gelatin (20%) in glycerin (70%) along with medicine (10%).
Primarily used for suppositories and medications.
PEGs are ethylene oxide and water polymers. A variety of molecular weights (300, 400, 600, 1000, 1540, 3350, 4000, 6000, and 8000) yield varied solid or liquid properties. Melting ranges increase with higher molecular weights.

Miscellaneous Bases

Chemical or physical mixtures of oleaginous and water-soluble substances.
Preformed emulsions (e.g., polyoxyl 40 stearate) are another option.

Displacement Value of Bases

Displacement value (DV) determines the weight portions of active ingredient that a base in a suppository displaces.
DV is often used to calculate the needed weight of base when making suppositories.
Typical DVs are shown against common medications used in suppositories.

Preparing Suppositories via Moulding

Melt the base and add the medication
Pour into a pre-made mold.
Allow the mixture to solidify.
Remove the suppositories.
Moulds made from steel, aluminum, brass, or plastic and lubricated with oils (like liquid paraffin) to ease removal.
Moulds need calibration and volume specifications, and often an extra amount of suppositories is made to account for losses.

Suppository Size & Content

Common suppository sizes are 1g and 2g.
Nominal sizes represent the base weight needed to fill the suppository mold; they don't reflect the actual final weight of the finished product.

Adding Solids/Liquids to Bases

Adding insoluble solids requires reducing their size (trituration) and including them in a portion of the melted base.
Stir well to ensure drug dispersal into the base.
Soluble solids are added directly and stirred well into the molten base.
Liquids are added to the molten base, followed by mixing until dispersed. If dealing with extracts, allow some cooling.

Suppository Shelf Life, Packaging, and Labeling

For stable products (suppositories and pessaries), storage at cool temperatures with proper packaging is crucial.
Typical shelf life is up to 4 weeks.
Materials like PVC or foil are common packaging materials.
Clarity in labeling (storage conditions, 'use only as directed', 'do not swallow', 'rectal' or 'vaginal use only', etc) is essential.

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Description

Test your knowledge on suppository formulation in pharmaceutical science. This quiz covers the characteristics, types, and considerations involved in creating effective suppositories. Assess your understanding of the essential ingredients and their properties.