Suppositories Flashcards
What are suppositories
solid dosage forms administered via body cavities, especially rectum and vagina. They are of certain shapes (tapered for rectal and globular or oviform for vaginal use) usually made using moulds.
What are pessaries for
for virginal use
Advantages of the rectal route
It can be used when the patients cannot use medicines orally
– Problems with the GI tract, e.g. vomiting, postoperative when the patient is still unconscious
– The paediatric population
– The geriatric population
• It can be used when the drugs are not suitable for oral use
– Side effects to the GI track
– Drugs not stable at the pH of the GI tract or due to enzymatic degradation
– Poor bioavailability due to the first-pass metabolism • The rectal route can be used for
– systemic delivery: the first pass metabolism by the liver can be avoided
– local delivery, such as pain and itching
Disadvantages of the rectal route
Poor patient acceptance in some countries
• Sometimes absorption is slow and erratic,with considerable inter- and Intra-subject variations
• Some of the excipients may be irritant to the rectum
• Leakage can be a problem
• Tend to have problems in large-scale production
• Stability problems, especially at high temperatures
Advantages of the vaginal route
The vaginal route can be used for
– local delivery-lower dose and lower toxicity(majority of applications belong to this group)
• Infections-Trichomonas and Candida infections,. E.g. miconazole, clindamycin, clotrimazole
• Contraception–spermicide such as nonoxynol-9
• Lubrication
– Systemic delivery,e.g.oestrogen,progesterone,andprostaglandin (vaginal cream or hydrogel). Higher bioavailability: first pass metabolism by the liver can be avoided
• The first uterine pass effect: drugs administered via the vaginal route are delivered preferentially to the uterus, and are suitable for uterine targeting, e.g. progesterone and danazol
• Avoids the harsh environment of the stomach
The vaginal wall is very good for drug absorption due to the rich net work of blood vessels.
Disadvantages of the vaginal route
• The vaginal route is gender specific
• Leakage is almost unavoidable (loosing dose and contamination of underwear)
• Patient compliance – culture dependent
• Menstrual cycle and hormonal variations affect the absorption of
drugs intended for systematic use
• Absorption may occur for medicines intended for local use (with undue side effects)
• Some excipients may cause irritation/discomfort
• Absorption can be affected by the varying volume of the vaginal
fluids
• Absorption can be affected by the pH of the vaginal fluids (normally acidic)
Physiology of the rectum - where is the rectum located and what is its length
The rectum forms the lower part of the GI tract and is about 15 to 20 cm long
Physiology of the rectum - describe the wall of the rectum
The wall of the rectum is relatively smooth and there is no villi. The rectum is empty under normal conditions
Physiology of the rectum - how much mucus is in the rectum
The mucus in the rectum is approximately 3ml spreading over a area of 300 cm2
Physiology of the rectum - what is the pH of the mucus
The pH of the mucus is approximately 7.5 with little buffer capacity
Physiology of the rectum - what do the lower, middle and upper veins do
The lower and middle veins in the rectum drain directly into the systemic circulation, bypassing the liver portal vein
• The upper veins drains into the liver via the portal vein
Factors affecting drug absorption from rectum
The absorption is a passive process
• Area of rectal wall (300 cm2) is significantly smaller than
that of the small intestine (about 200 m2, or 2x 106 cm2)
• Quantities of fluid available in the rectum is small
• Properties of the rectal fluid. This is mostly unknown and have to be estimated from data from other parts of the GI tract. Reported to be pH 7.5 with low buffer capacity
• Pressure from rectal wall (due to abdominal organs when the body is upright and the contraction of the colon wall). This helps spreading and promote absorption.
• No esterase or peptidase activity, hence better stability of peptide drugs
• Dosage forms
Physiology of the vagina - where is it located and what do the blood vessels do
Tubular structure connecting uterus to the external environment. Richnetworkofbloodvesselsleadingtoinferior vena cava, avoiding the liver portal systems
Physiology of the vagina - what is it coated with
Coated with vaginal fluid
– Acidic (pH3.5 -4.5)
– Varies significantly with age
– Affected by menstrual cycle, sexual activity – pH tends to rise due to local infection
Factors affecting drug absorption from vagina
Passiveprocess/transport • Age • The volume, viscosity, pH of the vaginal fluid– the pH is affected by local infections • Stage of the menstrual cycle • Sexual activity • Ionisation of drug molecules • Size of drug molecules • Dosage forms
