DD291247A5 - PROCESS FOR THE PREPARATION OF SUPPOSITORIES WITH IMPROVED DRUG DISTRIBUTION - Google Patents

Abstract

The invention relates to a process for the preparation of suppositories with improved active ingredient distribution. This method enables a homogeneous distribution of active ingredients in suppositories and is particularly suitable for the processing of highly sedimenting active ingredients. According to the invention, a glycerol stearate type emulsifier is incorporated at a specific concentration. Below and above this concentration, strong inhomogeneities occur. {Suppository preparation; Active substance strongly sedimenting; Drug distribution; emulsifier; glycerol stearate}

Description

Field of application of the invention

The invention relates to a process for the preparation of suppositories with homogeneous distribution of easily sedimenting active ingredients.

Characteristic of the known state of the art In the manufacture of suppositories, the uniform distribution of the active ingredient as in other dosage forms is an important one Demand. An exact dosage is only guaranteed if this quality criterion (content uniformity) is adhered to. Some active substances prove to be problematic substances in that they have particularly high content fluctuations and

a homogeneous distribution is not achievable with the usual methods. Therefore, there are numerous studies that deal with the elimination of this difficulty.

Of particular importance are the quality assurance measures in low-dose (low-concentration) systems. For example, in piroxicam suppositories, which generally contain 1% of active ingredient, strong salary fluctuations

observed.

As process improvements have been proven (B.W. Müller, Suppositories, Wiss. Verfagsges.mbH, Stuttgart 1986; K. Thoma, dosage forms for rectal and vaginal administration, advertising and sales. German Pharmacist, Frankfurt 1980)

The reduction of particle size and

- Increasing the viscosity in the melt of the suppository mass.

These two parameters are derived from the Stokes case law as the galenic variables that allow a rate of sedimentation to change. The particle diameter has a direct proportionality and the viscosity a reverse proportionality. In the case of aminophenazone, detectable sedimentation was avoided if the particle size was below 100 μm (W. Hennig, Dtsch. Apotheker-Ztg. 119, 102711979]). Additions of 1 to 2% adjuvant are often sufficient to influence viscosity increase. Consideration Aerosil, bentonite, aluminum stearate ^and glycerol stearate By 5% aluminum stearate, the viscosity of the bulked suppositories is measured at 40 ° C. even threefold and by 5% Aerosil or bentonite even increased by 12 to 20 times (R. Voigt, textbook of pharmaceutical technology, publisher Volk and Health, Berlin 1973).

Correspondingly, the sedimentation rate would have to decrease.

In several cases, however, it had to be stated that the factors mentioned above make it impossible to meet the requirements for the nature of suppositories. For example, piroxicam showed significant inhomogeneities at a particle size below 100 pm, and also viscosity increases did not succeed.

Object of the invention The aim of the invention is a method that ensures the uniform distribution of problematic drugs in suppositories. Explanation of the essence of the invention

The object of the invention is the development of a process for the production of high-quality suppository for strong sedimentation agents, which is carried out using excipients with emulsifier effect. After known methods proved unsuitable, an attempt was made to solve the problem with the help of emulsifiers. The incorporation of surface-active auxiliaries was also unsuccessful. In the case of piroxicam, the addition of 1 to 3% emulsifier 1102 (mixture of saturated mono-, di- and triglycerides, mainly glycerol monostearate) worsened the distribution of the active ingredient over the surfactant-free sample (see Table). Thus, this process variant appeared equally useless.

However, the situation changes fundamentally when the surfactant concentration is further increased. It has surprisingly been found that with the addition of 5% emulsifier 1102, the homogeneity increases sharply and is within a range that meets the requirements of international pharmacopoeias. Standard deviations from the results are shown in the Table.

table

Distribution of piroxicam in a series of 25 suppositories

(Requirement: 95.0 to 105.0% piroxicam)

sequence without addition emulsifier 3% 5% when casting 1% 101.0% 102.7% Beginning 85.9% 91.6% 102.1% 97.8% 87.8% 93.6% 77.2% 101.7% 89.3% 78.3% 80.4% 100.9% 90.5% 87.8% 107.9% 104.2% center 95.3% 79.1% 96.7% 102.4% 91.8% 74.5% 71.3% 97.2% 77.1% 102.8% 179.7% 105.0% The End 100.6% 175.0% 116.9% 99.0% 111.4% 104.4% 97.0% 98.9% 186.7% 117.9% 230.1% 101.5% 142.2% 42.2% 2.6% Srei. 28.0% 30.8%

For incorporation of the emulsifier about 90% of the suppository mass are heated with the emulsifier to 70%, so that the basis melts and the emulsifier swells. In a second approach, the active ingredient is mixed with the remaining 10% of the molten suppository mass. After combining both melts can be poured at 50 ⁰ C in molds.

In order to increase the effect, an attempt was made to further increase the emulsifier concentration. However, there was a high increase in viscosity and the inclusion of air bubbles. The concentration of 5% emulsifier 1102 thus represents an optimum in ROSUPOL (triglyceride base).

embodiment

20.0 g of finely powdered piroxicam with 180,0g ROSUPOL (Triglyceridgrundlage) melted at 50 ⁰ C and homogenized using an Ultra-Turrax. Besides 1700,0g ROSUPOL with 100.0 g Emulsifier 1102 (VEB oil Were Gotha) at 70 ⁰ C to be melted, wherein the emulsifier remains fixed and suspended in the melt is present. After cooling to about 5O ⁰ C, the two approaches are combined with stirring and thoroughly mixed. Finally, the pouring out of the mass takes place.

Claims (3)

1. A process for the preparation of suppositories with improved distribution of active ingredients, characterized in that an emulsifier of the type of saturated glycerol ester is incorporated in a concentration of 4 to 7% by in known manner about 90% of the suppository mass with the emulsifier to 70 ^0th C heated and in a second approach the   Active ingredient can be mixed with the remaining amount of molten suppository mass. 2. The method according to claim 1, characterized in that it is used as the active ingredient piroxicam. 3. The method according to claim 1, characterized in that a mixture of saturated mono-, di- and triglycerides, mainly glycerol monostearate is used as the emulsifier.