Suppositories bioavailability

Suppository Bioavailability is 25% lower than with oral formulations. Licensed only for short-term use. Unlikely to be suitable for... 

Choi HK, Oh YK, Kim CK. In-situ gelling and mucoadhesive liquid suppository containing acetaminophen enhanced bioavailability. Int J Pharm 1998 165 23-32. 

The pharmaceutical properties of artemisinin are far from optimal it is insoluble in water and only marginally soluble in oil. It has poor oral bioavailability and has been administered for the treatment of Plasmodium falciparum malaria in humans at total doses of about 1 g (over 3 days). Early studies by Chinese scientists in 1979 led to the discovery of dihydroartemisinin 3, artemether 4 (Artenam), and sodium artesunate 5, oil and water soluble derivatives, respectively (Figure 9.1 ).6-7 These drugs are currently in clinical use in Asia in a number of preparations such as suppositories, i.v. injectables, oil depos, to name only a few.8 Capsules containing 0.5 g of artemisinin for oral administration are available in Vietnam. 

Tramadol is available as drops, capsules, and sustained-release formulations for oral use, suppositories for rectal use, and solution for intramuscular, intravenous, and subcutaneous injection. After oral administration, tramadol is rapidly and almost completely absorbed. Sustained-release tablets release the active ingredient over a period of 12 h, reach peak concentrations after 4.9 h, and have a bioavailability of 87 to 95% compared with capsules. One 100-mg dose given to healthy volunteers resulted in plasma levels of 375 ng/ml at 1.5 h.55 Tramadol is 20% bound to plasma protein and it is rapidly distributed in the body it is mainly metabolized by O- and A-demethylation forming glucuronides and sulfates that are excreted by the kidney. 

Topical bioavailability can be improved by the enhanced release of a drug from ointment or suppository bases. 

Watanabe, Y., et al. 1986. Pharamaceutical evaluation of hollow type suppositories. IV. Improvement of bioavailability of propranolol in rabbits after rectal administration. J Pharmacobiodyn 9 526. 

FIGURE 8.3 Bioavailability of morphine after rectal administrations of Witepsol H-15 hollow-type suppositories containing morphine hydrochloride (MH) and CyDs in rabbits. Each value represents the mean SE of three rabbits. p < 0.05, compared with MH alone. 

Nakanishi, K., et al. 1994. Improvement of the rectal bioavailability of latamoxef sodium by adjuvants following administration of a suppository. Biol Pharm Bull 17 1496. 

Administered orally, ergotamine and sumatriptan have only limited bioavailability. Dihydroergotamine may be given by i.m. or slow i.v. injection, sumatriptan subcutaneously, by nasal spray, or as a suppository. When given orally, other triptans such as zolmitriptan, naratriptan, and rizatriptan have higher bioavailability than sumatriptan. 

Morphine Pain control as alternative to parenteral administration Tablet and vaginal suppository Requires close monitoring due to unpredictable bioavailability 337... 

Biopharmaceutic considerations in the design and manufacture of a drug product to deliver the active drug with the desired bioavailability characteristics include 1) the type of drug product (e.g., solution, suspension suppository) 2) the nature of the excipients in the drug product 3) the physicochemical properties of the drug molecule and 4) the route of drug administration. 

Hosny, E.A. Al-Angary, A.A. Bioavailability of sustained release indomethacin suppositories containing polycarbo-phil. Int. J. Pharm. 1995, 113, 209-213. 

Tukker JJ, De Blaey CJ. The addition of colloidal silicon dioxide to suspension suppositories II. The impact on in vitro release and bioavailability. Acta Pharm Technol 1984 30 I55-I60. 

Yun M, Choi H, Jung J, Kim C. Development of a thermo-reversible insulin liquid suppository with bioavailability enhancement. Int J Pharm 1999 189(2) 137-145. 

Taylor JB, Simpkins DE. Aminophylline suppositories in vitro dissolution and bioavailability in man. Pharm J 1981 111-. 601— 603. 

Dmgs administered by the rectal route in suppositories are placed in intimate contact with the rectal mucosa, which behaves as a normal lipoidal barrier. The pH in the rectal cavity lies between 7.2 and 7.4, but the rectal fluids have little buffering capacity. As with topical medication, the formulation of the suppository can have marked effects on the activity of the drug. Factors such as retention of the suppository for a sufficient duration of time in the rectal cavity also influence the outcome of therapy the size and shape of the suppository and its melting point may also determine bioavailability. 

Rgure 9.53 Schematic representation of rectal absorption of an active principle from a suppository, and the factors at each stage likely to affect the bioavailability of the drug. Modified from F. Jaminet, in The Suppository (ed. B. R. Guillot and A. P. Lombard), Maloine, Paris, 1973. 

In a smdy of the various physical properties of suppositories, the most important parameter for the bioavailability of paracetamol was found to be their rheological properties at 37°C. The relationship between the excretion of paracetamol (APAP N-acetyl-p-aminophe-nol) and the rheology of the excipient dmg suspension is shown in Fig. 9.55. The greater the limiting shear stress, r, of the system, the lower the bioavailability of the dmg. 

Bioavailability enhancer Tablets, capsules, granules, pellets, suppositories, transder-mal systems... 

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