suppository
A suppository or suppository (from cones , pharmaceutically “Walger, Rolle”) is a dosage form that is intended for insertion into body cavities such as the rectum ( rectal suppository , anal suppository ) or the vagina ( vaginal suppository , vaginal ovula or vaginal suppository ) .
Reasons for using
In contrast to oral dosage forms such as tablets , suppositories can also be used when absorption through the mouth and gastrointestinal tract is not possible. This can affect patients who have difficulty swallowing, unconscious patients, or unwilling people such as young children. In addition, the first-pass effect is partially circumvented when used rectally . Unlike after absorption in the stomach and small intestine, in which the active ingredient reaches the liver via the portal vein system, where it may be broken down before it can take effect, the rectum only partially discharges its venous blood through the liver. The reason for this is that both the inferior rectales and media rectal veins have access to the inferior vena cava via the iliac veins . The Vv. Rectales superiores open out via the V. mesenterica inf. into the V. portae hepatis . A longer-lasting depot effect can also be achieved when used in the rectum. In addition, suppositories are also used for hemorrhoidal disorders when a local effect of the suppository in the rectum is desired.
application areas
Typical areas of application for rectal suppositories are, for example, vomiting diseases such as acute gastroenteritis , since absorption via the mucous membrane of the intestine takes place quickly, so that even with diarrhea , a sufficient amount of active ingredient can often get into the bloodstream. In the case of migraines and the impairment of gastric emptying that usually occurs there , the administration of an analgesic suppository is useful. In children, suppositories are usually also used to treat pain and lower high fever, e.g. B. Paracetamol administration and the treatment of vomiting disorders . A laxative can also be administered in the form of a suppository to empty the rectum.
Vaginal suppositories are used to treat gynecological diseases such as thrush colpitis , but also to relieve micturition problems such as stress incontinence , which can arise from a lack of estrogens and the atrophy of the vaginal membrane and the underlying connective tissue structures. Furthermore, spermicidal suppositories can be used for contraception .
The system for inserting into the urethra for the purpose of treating erectile dysfunction ( MUSE , with the active ingredient alprostadil ), which is pharmaceutically classified as rods, is sometimes also referred to as "mini suppositories".
administration
In general, rectal suppositories are best inserted into the anus after a bowel movement . To improve the lubricity, the suppositories can be warmed in the hand or briefly dipped in warm water.
There are different opinions as to whether the suppository should be inserted into the anus with the pointed or the blunt side first. In general, the instruction leaflet usually describes insertion with the pointed end first. However, the medical literature often recommends introducing it blunt end first. This is justified by the fact that the rectal mucosa can better attach itself to the tip and the uvula slides more easily into the rectum in this way. A study on adults and children showed that suppositories inserted blunt side first are also less likely to be pushed out of the rectum. In addition, in toddlers and infants, gently squeezing the buttocks should prevent them from being squeezed out again.
Manufacturing
In addition to industrial production, suppositories are one of the drug forms that have been used for a long time, which are still produced manually in the pharmacy and individually for a patient according to the doctor's specifications.
Basics
In the case of suppositories, a distinction is made between water-soluble and fat-containing preparations. The most common starting substance for fatty bases is hard fat with a melting range close to human body temperature, made from a semi-synthetic mixture of mono-, di- and triglycerides . Hard fat is obtained from palm kernel and coconut fat through saponification and subsequent hydrogenation of unsaturated fatty acids . The main component is lauric acid, which is obtained by distilling the fatty acid mixture. After re- esterification with glycerol , hard fats with defined emulsion and melting properties are obtained. The more free OH groups a certain type of hard fat has, i. H. the higher their hydroxyl number , the higher their property of forming water-in-oil emulsions . Conversely, hard fat becomes more brittle the lower its hydroxyl number. Adeps solidus , as the old Latin technical term is, goes rancid much more slowly due to the lack of unsaturated fatty acids in contrast to the cocoa butter used in the past .
In contrast to fat-containing suppositories, water-soluble suppositories should not melt at body temperature , but rather dissolve in the water present at the application site and release the active ingredient. The problem is the very small amount of fluid in the rectum, for example, in which the suppository is supposed to dissolve. However, with these so-called “tropical suppositories”, starting materials with a melting point higher than body temperature can be used, which makes them interesting for use in warmer climates.
Mixtures of different polyethylene glycols with a melting range between approx. 55 and 60 ° C are used for rectally applied suppositories. For vaginal suppositories, a mixture of gelatine and glycerol is usually used, which, however, is susceptible to microorganisms without the addition of preservatives .
production method
Suppositories are mainly produced using the casting process, in which the active ingredients and hard fat are melted together and then placed in a metal mold. A pressing process is also used less frequently. Depending on the substances used, the melt is a suspension , emulsion or solution .
In the case of prescription-based or defective production in the pharmacy, there are two methods of determining the necessary mass of suppository base in order to obtain the corresponding number of suppositories with the prescribed amount of medicinal substance. By pouring out the suppository mold , you get the calibration value of the mold , i.e. the average mass of a suppository of the base used. Adult suppositories weigh about two grams , child suppositories about one gram, and vaginal ovules about three grams.
In the Münzel method , the medicinal substance is melted with slightly less than the amount of suppository base required for all suppositories and placed in the mold. Then the form is completely filled with pure foundation. The suppositories obtained in this way are melted down again in order to distribute the medicinal substance homogeneously and are filled into the mold again.
The displacement factor method takes into account how much volume the drug substance used displaces in terms of base. These displacement factors are tabulated for many substances and can also be determined experimentally. The required amount of base is calculated from the mass and number of suppositories, as well as from the amount of medicinal substance and its displacement factor.
In the pressing process, the grated base mass and medicinal substance are mixed and pressed in a special press in the shape of a suppository or stick. This process is suitable both for preparations containing hard fat and for bases based on polyethylene glycols.
In order to ensure a melting range of 33 to 36 ° C, i.e. slightly below body temperature, in suppositories, the lowering of the melting point of a medicinal substance must be compensated for by the appropriate selection of a type of hard fat with a correspondingly lower or higher melting range. If the melting range was too low, the suppository would not be dimensionally stable enough; if the melting range was too high, it would not release any active substance at body temperature.
See also
literature
- Kurt H. Bauer, Karl-Heinz Frömming, Claus Führer, Bernhardt C. Lippold: Textbook of Pharmaceutical Technology . 8th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart 2006, ISBN 3-8047-2222-9 .
- Rudolf Voigt, Alfred Fahr : Pharmaceutical Technology . 9th edition. Deutscher Apotheker Verlag, Stuttgart 2006, ISBN 3-7692-2649-6 .
Web links
Individual evidence
- ↑ Jürgen Martin: The 'Ulmer Wundarznei'. Introduction - Text - Glossary on a monument to German specialist prose from the 15th century. Königshausen & Neumann, Würzburg 1991 (= Würzburg medical historical research. Volume 52), ISBN 3-88479-801-4 (also medical dissertation Würzburg 1990), p. 194.
- ↑ Wolfgang Kirchner: Using dosage forms correctly . 2nd Edition. Deutscher Apothekerverlag, Stuttgart 2000, ISBN 3-7692-2767-0 . Page 250f.
- ↑ Abd-el-Maeboud KH et al. Rectal suppository: commonsense and mode of insertion . Lancet. 1991 Sep 28; 338 (8770): 798-800. PMID 1681170 .
- ↑ Paul Diepgen : The anal suppository in the history of therapy. Stuttgart 1953.
- ↑ Otto Nowotny: On the history of the suppository. In: Österreichische Apotheker-Zeitung 8, 1954, pp. 539-542.
