PROMISING STUDIES AND NEW APPLICATIONS

BIOADHESIVE COMPOSITIONS

These formulations can facilitate the maximum drug release and adsorption of the active principle both for rectal and vaginal administration. The bioadhesive added to the formulation, allows the active principle to be adsorbed locally and with higher efficiency. Bioadhesives are natural polymer compounds that act as adhesives. The term covers a broad range of substances: some, such as gelatine, have been used by man for many years (and in many cases have been superseded by synthetic alternatives); others are not yet in commercial use. Bioadhesives are biocompatible and can work in wet environments and under water Different polymers are used as bioadhesive but their main property is to stick to the internal membrane of vagina or rectum. Here some application example:

RECTAL AND VAGINAL SUPPOSITORIES CONTAINING BIOADHESIVE BROMOCRIPTINE AND POLOXAMER (WO 2006/099877)

Trials of vaginal use of the commercial tablets resulted in significant decline of the prolactin level after 1 month of therapy. However, the patient acceptability was very low as they were convienced that tablets can be effective if inserted vaginally. Many patients feel that the previous formula was inconvenient due to excessive vaginal discharge and easy dislodgement from the vagina. In the current modification, the previous formula is mixed with bioadhesive polymers including caobopol 974P, chitosan and is created in a suppository form suitable for both male (rectal) and female (vaginal) usage to extend the scope of this treatment modality.

SUPPOSITORY COMPOSITION OF THE DRUG WHICH UNDERGO THE HEPATIC FIRST-PASS EFFECT (WO 1997/030693)              

This study relates to a suppository composition containing a drug which undergoes the hepatic first-pass effect, poloxamer and hydrophilic natural polymers. The suppository composition of this invention is characterized in that: has the gelation temperature of 30 to 36 °C, and is a liquid form at room temperature, and readily becomes a gel at body temperature after rectal administration; has the remarkable gel strength, and is not leaked out the anus; has the remarkable bioadhesive force, and doesn't climb up to the end of the colon, therefore ensures better bioavailability of the drug.

ADSORBTION ENHANCERS

Many peptides and some antibiotics can't be administered orally because they are degraded by enzymatic reaction and/or they are not adsorbed with the rapidity necessary in order to have the effective therapeutic concentration. For this reason it's widely used the parental way, but also the rectal way can avoid enzymatic or chemical degradation before the adsorption. In order to improve the adsorption of peptides and antibiotics in rectum, many studies have shown the efficacy of chemical substances called "adsorption enhancers" in the drug delivery through the rectal membrane. Here some application example:

SUPPOSITORIES CONTAINING MISOPROSTOL (WO 2006/125450)

Misoprostol is commonly used in obstetric practice for controlling post-partum and post-abortive bleeding, and inducing labor or abortion whenever indicated. Commonly, misoprostol is administered orally. Tests have been carried out to study the behaviour of the commercial tablets when administered sublingually, rectally or vaginally. However, the application of said tablets, either vaginally or rectally, in their current form is not easy, as the tablets are designed for oral use. A recent study show that misoprostol-containing suppositories are more convenient, if used rectally resp. vaginally. Additionally, the suppositories contain at least one poloxamer to enhance absorption and at least one bioadhesive compound.

OTHER NEW DEVELOPMENTS IN SUPPOSITORY ADMINISTRATION

ANTIBIOTICS BY RECTAL ROUTE

Different researches on animals have shown that goods results in the adsorption of antibiotics on suppository form can be obtained by the use of adsorption enhancers (Bergogne-Berezin E., Bryskier A. - The suppository form of antibiotic administration: pharmacokinetics and clinical application, -J. Antimicrob. Chemoter. 1999 Feb, 43(2): 177-85).

INSULINE BY RECTAL ROUTE

In 1989 a study has shown the effectiveness if insulin suppositories in diabetic patients. A from containing insuline, sodium salicylate and lecithin can avoid post-meal glycemia if the administration is 15 minutes before a normal meal (Nishihata T., Kamada A., Sakai K., Yagi T., Kawamori R., Shichiri M. - Effectiveness of insulin suppositories in diabetic patient - J. Pharm. Pharmacol. 1989 Nov, 41(11): 799-801).

MALARIA

The Malaria is a parasitary disease transmitted by the bite of female anopheles mosquito. At present it is estimated that 40% of the world population mainly in the developing countries is exposed to Malaria. This disease is present in the tropical and sub-tropical areas and is responsible of more than 500 millions cases each year, the majority of deaths being in the sub-saharian Africa. The Artesunate molecule derived from Artemisia annua L. has been shown to be very effective against Malaria with a powerful schizonticide activity, with fever and parasites disappearing in peripheral blood within 24-56 hours. A study of the bio-availability of Artesunate show that rectal route is a very interesting alternative to parenteral route. It allows an easy urgency treatment, without the need of qualified personnel or very good hygienic conditions, so the patient has the time to be delivered to hospital for a more accurate treatment (Vu Thi Pan, L'artémisine et l'artésunate dans le traitement du paludisme au Vietnam (1984-1999), Bull. Soc. Pathol. Exot., 2002,95,2,86-88).

IMMUNIZATION BY RECTAL ROUTE: STUDY ON TUBERCOLOSIS

Tubercolosis kills 2 millions of people each year in the world. Today the prevention of this disease uses the BCG, developed by Institut Pasteur in 1921. It is effective in 90% of the cases to prevent serious illness in infant age, but for adults the protection remains uncertain. Recent studies on the administration of BCG by rectal route to monkeys have shown that specific immune response is similar to subcutaneous or intra-dermic administration, but it's less expensive and allows a reduction of the risks connected with the use of syringes in developing countries

(http://www.pasteur.fr/actu/presse/com/communiques/04JourneeMondialeTuberculose.html).

SUPPOSITORIES SUSTAINED IN THE LOWER RECTUM (WO 2002/024161)

Suppositories sustained in the lower rectum characterized by containing a suppository base which comprises: (A) a fatty acid triglyceride; (B) one or ore glycerol fatty acid esters having 14 to 18 carbon atoms; and (C) a base component sustained in the lower rectum. When held with fingers before inserting into the rectum, these suppositories would not melt due to the body temperature of the fingers and thus can be easily handled. Moreover, they suffer from no deformation due to an increase in temperature during storage and would not irritate the rectal mucosa, thereby causing no congestion, bleeding, enlargement, etc. Namely, these suppositories are highly safe.

UROGENITAL OR ANORECTAL TRANSMUCOSAL VACCINE DELIVERY SYSTEM (WO 2001/064186)
The invention is directed to a suppository based vaccine delivery system for immunizing against urogenital and anorectally transmitted infectious disease in humans and animals and a method for treating the same. More particularly, this invention is directed to a suppository based vaccine delivery system for the prophylaxis against or treatment of urogenital or anorectal transmitted infectious diseases, such as from viral or microbial pathogens. The suppository based delivery system comprises vaccine and/or vaccine adjuvant(s) comprised of whole or fractionated viral or other microbial pathogens, or their purified cellular constituents, whether native, mutated, synthetic, cloned or recombinantly expressed, that consists of nucleic acids, pro...

CONCLUSION

Rectal administration is yet to be truly explored as a potential for drug delivery in many institutional settings and non-institutional settings for drugs that are either too irritating to the gut or are more effective if not metabolized by the liver. For both scientific and economics reasons we should really consider rectal administration to be a viable and valuable option. Suppositories offer patients an option that is less invasive and less discomforting.