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30 Cards in this Set
- Front
- Back
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What are the 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 |
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What types of delivery can the rectal route be used for? |
– systemic delivery: the first pass metabolism by the liver can be avoided– local delivery, such as pain and itching |
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What are the disadvantages pf 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 |
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Which types of delivery can the vaginal route be used for? |
• 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, and prostaglandin (vaginal cream or hydrogel). Higher bioavailability: first pass metabolism by the liver can be avoided |
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Why do vaginal drugs bypass the first pass effect? |
The first uterine pass effect: drugs administered via the vaginal route aredelivered preferentially to the uterus, and are suitable for uterinetargeting, e.g. progesterone and danazol• Avoids the harsh environment of the stomach |
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Why is the vaginal wall very good for drug absorption? |
The vaginal wall is very good for drug absorption due to the rich net work ofblood vessels. |
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What are the disadvantages of the vaginal route? |
• The vaginal route is gender specific• Leakage is almost unavoidable (losing 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 |
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How long is the rectum? |
About 15-20cm long. |
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What are the features of the rectum? |
-Wall is smooth and there are no villi -Empty under normal conditions -Mucus in the rectum is approximately 3mL, spreading over the area of 300cm^2 -pH of mucus is approximately 7.5, little buffer capacity |
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Where do the lower and middle veins of the rectum drain? |
-Lower and middle veins in the rectum drain directly into systemic circulation, bypassing the liver portal vein |
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Where do the upper veins of the rectum drain? |
Into the liver via the portal vein |
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Which factors affect drug absorption from the 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 form |
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What connects the uterus to the external environment? |
A tubular structure |
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What is the vagina coated with? And what are its features? |
Vaginal fluid: -Acidic (ph3.5-4.5) -Varies significantly with age -Affected by menstrual cycle and sexual activity -pH tends to rise due to local infection |
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Why is the liver portal system avoided using the vaginal route? |
There is a rich network of blood vessels leading to the inferior vena cava. |
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What factors affect drug absorption from the vagina? |
• Passive process/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 |
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How are suppositories manufactured? |
• Melt the base• Add drug into the base and mix• Keep the temperature as low as practically possible. If too high:– Drug stability issues– The drug/base mixture becomes too thin (viscosity too low)– It takes longer for the base to set and the drug may settle during this time• Pour the drug/base mixture into mould. Over fill the mould to allow shrinkage on cooling• Cool at controlled rate to let the mixture set• Scrap of the excess• Remove the suppositories |
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What are the quality control meaures in place for suppositories? |
• Dose uniformity• Weight uniformity• Mechanical strength• Content uniformity• Disintegration• Drug dissolution/release• Temperature normally set at 37 ˚C. However, body temp can be as low as 36 ˚C at night and therefore the release rate can be an over estimate• Contact area. The actual testing area is about 10 cm2, so it is difficult to simulate the real situation (300 cm2). It can only be used for comparative studies• Medium. Difficult to simulate |
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What are the requirements of the vehicles and bases for suppositories? |
• Must melt after inserted into the body, or dissolve in the fluid in the cavity• The melting range should be just below 37˚C• The melting range should be small enough for rapidsetting when cooled during manufacturing, but not too small, to prevent fissures during rapid cooling• During solidification, the base should have enough volume contraction for ease of removal of thesuppositories • The molten base should have suitable viscosity• If too thin, the drug particles will settle too fast during preparation• If too viscous, it may be difficult to pour into the mould• The viscosity will affect how efficiently the vehicle is spreadwithin the body cavity, and how fast the drug molecules can be transported through thevehicle on to the cavity wall for absorption• Chemically and physically stable during storage• Allow satisfactory drug release |
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Which lipid bases are used for suppositories? |
-Cocoa butter (theobroma oil, a mixture of triglycerides) -Semi-synthetic lipids |
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What are the features of cocoa butter? |
Polymorphic behaviour• beta‐form: melting point 34.6°C (if melt at 36°C and cooled slowly)• alpha‐form: melting point 23°C (if over heated and/or cooled quickly)• gamma‐form : melting point 19°C (if over heated and cooled quickly)– The alpha‐ and gamma-form will eventually change to the stable beta-form,but may take several days– Poor chemical stability (contains unsaturated fatty acids)– Low softening point– Insufficient contraction at cooling |
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What are the features of semi-synthetic lipids? |
– Mixture of triglycerides with C12‐C18– Saturated fatty acids (more stable than the natural ones with unsaturated fatty acids)– Melting temperature is a few degrees higher than cocoa butter |
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What is the hydroxyl number and what does it mean? |
Relates to the amount of mono‐ and diglycerides in the base. A high number means that:– the base is more polar and can absorb more water– the base tends to have wider melting range (temperature)– the base may lead to the formation of w/o emulsions, which may retard drug release/absorption |
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Which water-miscible bases are used for suppositories? |
• Glycerol‐gelatin base– Water : glycerol : gelatin 10 :70: 20 (can be adjusted)– Mostly used for the vaginal route or for laxative purpose– Gelatin content may need to be increased if used for the rectum route (so that the suppository becomes harder)• Polyethylene glycols of different molecular weight– Melting point is well above body temperature, so mixing with body fluid is the main mechanism of drug release– Irritant to the rectum due to water attraction from the mucous/membrane (osmotic pressure?). This can be relieved by:• incorporating 20% water• moistening the suppository before insertion |
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What has to be considered when formulating suppositories? |
-The drug solubility in the base (determines if the product is going to be from a solution or suspension and the emulsion type- w/o isn't recommended) -Surface property (surfactants and wettability- surfactants help the drug disperse homoheneously in the base and help the drug dissolbe in the mucous) -Particle size of drugs (small particles settle slower-> suppository needs to be homogeneous before base becomes solid-> smaller=less irritant to the cavity membranes) |
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How are moulds calibrated/ the capacity of them confirmed? |
Confirmed by filling the mould with the molten base and then the average weight of theperfect suppositories thus produced are calculated. This value is the calibration value for that particular base • In other words, the calibration value is the weight of a blank suppository (base only) |
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How is the displacement value of a drug calculated? |
Displacement value= Weight of drug/Weight of base displaced |
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How do you calculate the amount of base needed for suppositories? |
Amount of base needed for a number (N) blank suppositories = N x Y (Y is the calibration value, the weight of a blank suppository) |
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How do you calculate the amout of base needed is a drug of dose, D, is added? |
Amount of base needed= N x Y - N x D/DV N= number of blank suppositories Y= calibration value D= dose of drug V= volume displaced |
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What weight of Glycerol-Gelatin suppositories occupy the same volume as 1g of theobroma oil? |
1.2g |
