University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third … · 2017-05-22 · 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 4 Rectal drug delivery

University of Sulaimani School of Pharmacy

Dept. of PharmaceuticsThird level - Second semester

5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 1


Outlines

• Why rectal or vaginal route?

• Suppository

• Types of suppository base

• Glyceride-type fatty bases

• Water-soluble bases.

• Manufacturing

• Vaginal drug delivery


Why rectal or vaginal route?

• The patient is not able to make use of the oral route (unconscious, nausea).

• The drug under is not well suited for oral administration (acid sensitive, first pass

effect)

• Where localized treatment of either the rectum or vagina is required.

• Drawback

• These routes are generally disliked by patients


Rectal drug delivery

• Local action: This is desired or the local treatment of pain and itching, mostly due to

the occurrence of hemorrhoids (painful, swollen veins in the lower part of the

rectum and anus).

• Antiseptics, local anesthetics, vasoconstrictors, anti-inflammatory and laxatives.

• Systemic action:

• Anti-asthmatic, anti-inflammatory and analgesic drugs

• Diagnostic purpose


• Rectum is part of the colon, forming the final 15–20 cm of the GIT.

• The total volume of mucus is approx. 3 mL.

• pH is about 7.5

Absorption of drugs from rectum

• The lower and middle rectal (inferior and middle

hemorrhoidal) veins drain into the interior vena cava

→the heart and general circulation.

• The upper rectal (superior hemorrhoidal) vein drains

into the portal vein → the liver → the heart.

• Bioavailability will be low for certain drugs.


Outlines


• Suppository




• Manufacturing



Suppositories

• Suppositories are the primary, dosage form used for the administration of drugs via

the rectal route.

• They are single-dose preparations with a shape, volume and consistency appropriate

for rectal administration.

• Others that should be inserted into body orifices like urethra is called bougies

• Rectal suppositories are usually about 1–4 g

• Cylindrical bullet shape.

• They contain one or more active substances dispersed or dissolved in a suit able base

that may be soluble or dispersible in water or may melt at body temperature.


Suppository cont.

• Depending on the character of its vehicle, a suppository will either dissolve in the

rectal fluid or melt on the mucous layer.

• Dissolution of the complete vehicle will be difficult and requires extra water.

• Unpleasant sensation for the patient

• Absorption of drug from the rectum is primarily by passive diffusion

• The rate and extent of drug absorption is lower than the oral route


Outlines


• Suppository




• Manufacturing



Suppository base

• An ideal suppository vehicle or base should remain solid at room temperature and

melt, dissolve or disperse at body temperature.

• It should be non-irritating, physically and chemically stable, and pharmacologically

inert.

• It should be convenient to handle

• It should contract slightly on cooling to release itself from the mold with requiring

mold lubricants

• Less leakage


Fatty base

• They are fully or semi-synthetic.

• Theobroma oil (also known as cocoa butter) –a very commonly used base –

• It melts at 30°C to 36°C

• It is no longer used because of its many disadvantages in practice, such:

• Its polymorphic behavior

• Insufficient contraction during cooling,

• Low softening point,

• Poor water absorptive power

• Expensive.


Fatty base cont.

• Commercial examples include: Cotmar, Fattibase, Suppocire and Witepsol.

• These are mixtures of natural or synthetic vegetable oils and fatty alcohol.

• High hydroxyl number

• Less hydrophobic

• High hydroxyl number → high melting point → easier manufacturing


Water-soluble base

• Hydrophilic water-soluble (or miscible) vehicles are much less frequently used.

A. Glycerinated gelatin is a mixture of glycerol, gelatin and water.

• The mixture forms a translucent, gelatinous mixture, dispersible in the rectum.

• A higher proportion of gelatin in the mixture makes it more rigid and longer

acting.

• They are mostly used for laxative purposes

• They are hygroscopic and require well-closed containers


Water-soluble base cont.

B. Polyethylene glycols (macrogol):

• They consist of mixtures of polyethylene glycols of different molecular weight.

• Their melting point is higher than body temperature e.g. PEG 8000 (60°C to

63°C).

• PEGs are miscible with water and release the drug by diffusion.

• They are hygroscopic → uncomfortable sensation of the patient.

• Incorporation of 20% of water and moistening before insersion.

• Poloxamers (Pluronics) are water-soluble, copolymers with a wide range of uses


Drug release

• Suppository either dissolve or melt in the rectum.

• If the release from the dosage form is considered as the rate-limiting step.

• The tendency to remain in the base should be lowered as much as possible

Solubility in Choice of the vehicle

Fat water

Low High Low

HighLow Low

Fatty baseAqueous baseNot determined


Outlines


• Suppository




• Manufacturing



Manufacturing

• Manufacturing the suppositories and pessaries are similar in both cases and involves:

• Melting of the vehicle

• Mixing the drug and the molten vehicle

• Dispensing the liquid into a shape former (molding)

• Cooling to solidify

• Packing in the final container.


Manufacturing cont.


Manufacturing cont.

• Depending on the formulation, suppository molds may require lubrication before the

melt is poured to facilitate clean and easy removal of the molded suppositories

• Lubrication is not necessary when the base is cocoa butter or polyethylene

glycol

• Lubrication is usually necessary with glycerinated gelatin


Outlines


• Suppository

• Manufacturing


• Pessaries

• Vaginal tablets

• Vaginal films

• Vaginal rings


Vaginal drug delivery

• Vaginal delivery is used for both local and systemic effects.

• Local effect

• Anti-infectives, like clotrimazole, miconazole, clindamycin.

• Contraceptive (spermicide) like nonoxynol-9

• Hygiene and lubrication

• Drugs administered for local action in the cervico-vaginal area are not required to be

absorbed.

• Systemic effect

• Drugs given by intravaginal route have a higher bioavailability compared to the

oral route.

• E.g. oestrogens, progesterone and prostaglandin analogues


Vaginal drug delivery cont.

• Drugs designed for systemic action are absorbed by passive transport.

• Vaginal dosage forms include pessaries, liquids (vaginal solutions, emulsions,

suspensions), semi-solids (creams, gels, ointments), solids (vaginal tablets, films,

capsules and rings), spray and foams.

• Semi-solid formulations can serve dual purposes of providing medication as well as

lubrication.


Pessaries

• Pessaries are solid, single-dose preparations or vaginal insertion.

• Pessaries can be prepared in various shapes, usually ovoid

• Most often prepared with glycerol-gelatin bases

• Polyethylene glycols are less common, since they are said to promote irritation.


Vaginal tablet

• Vaginal tablets are solid, single-dose preparations.

• Vaginal tablets can be prepared in various shapes, ovoid being the most popular

• Excipients are used to improve the disintegration of vaginal tablets, e.g. a

bicarbonate together with an organic acid, which results in CO2 release.

• A good filler for vaginal tablets is lactose


Vaginal films

• Vaginal films are thin layers of a polymeric material, which are designed to dissolve in

the vaginal fluids and release the drug.

• Vaginal contraceptive film (VCF), containing nonoxynol-9

• It should be inserted one an hour before sex

• Vagina should not be washed for at least 6 hour after sex.

• Both vaginal tablets and films can be designed to include

bioadhesive polymers such as Carbopol and xanthan

gum.


Vaginal rings

• Vaginal rings offer the flexibility of controlled release of the drug over a prolonged

period of time.

• An example of vaginal ring is NuvaRing®, containing estrogen and progestin, used as

a contraceptive.

• It should left in the vagina for three weeks

• Acts for one month.


Documents

University of Sulaimani School of Pharmacy Dept. of Pharmaceutics Third … · 2017-05-22 · 5/21/2017 Pharmaceutical Compounding, Dr. rer. nat. Rebaz Ali 4 Rectal drug delivery