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of propiverine-hydrochloride and 49.8% of citric acid, deter› mined according to the method described in Example 6. The molar ratio of active agent to citric acid was 1 :5.6. 

240 mg of the thus obtained pellets each, corresponding to 45 mg propiverine-hydrochloride were filled into hard gelatine capsules and used for the bioequivalence study of Example 15. 

The release of propiverine from the pellets was carried out under the conditions as described in Example 5. The results are listed in the Table provided there. 

2400 g spherical citric acid cores which were produced in the same manner as already described in Example 3.2 were coated in a fluidised bed at an air feed temperature of 40-7 4 ° C. with a suspension consisting of 48 g Eudragitfi S 100, 48 g Eudragit Ll00, 13 g triethylcitrate, 65 g microfine talcum, 1860 g isopropanol and 200 g water. 20 

2500 g of the thus obtained retarded starter cores were sprayed under the same technical conditions with a suspen› sion of 828 g propiverine base, 177 g polyvinylpyrrolidone (Kollidonfi K25), 63 g citric acid, 200 g microfine talcum and 32 g magnesiumstearate in 3100 g 2-propanol and 400 g water. The total amount obtained was 3740 g active agent pellets corresponding to 98.4% of the theoretical amount, referring to the dry substance used. 

In the same manner 3250 g of the active agent pellets were sprayed with a suspension of720 g Eudragitfi RL 12.5 (90 g dry mass Eudragitfi RS), 368 g Eudragitfi RL 12.5 (46 g Eudragitfi RL dry mass), 90 g Eudragitfi Sl00, 24 g trieth› ylcitrate and 146 g micro fine talcum in 1930 g 2-propanol and 300 g demineralised water. 

3500 g of thus obtained retarded active agent pellets were sprayed in the fluidised bed under identical conditions with a suspension consisting of 86 g Eudragitfi S 100, 9 g triethyl› citrate, 52 g microfine talcum, 129.9 g 2-propanol and 80 g water. 

The thus obtained pellets showed a content of 19.4% propiverine as well as a content of 40.4% citric acid as deter- 

## Pellet Formulation with Propiverine 

## Example 4 

<img src='content_image/939410.jpg'>

mined by the methods described in Example 6. This results in a molar ratio of active agent to citric acid of 1 :4.0. 

The release of propiverine from the pellets was determined by the method described in Example 5 and is indicated in the Table provided there. 

## Determination of the Release Data-Comparison of the Release Data of Examples 1-4, 7-13 

The determination of the release of propiverine-hydrochlo› ride orpropiverine, respectively, from all of the described oral dosage forms was made with the help of the basket apparatus as described in Ph. Eur. 3, 2.93 at 100 rpm for 17 hours. 

For this an amount of pellets corresponding to 45 mg propiverine-hydrochloride each was weighed into 6 baskets. The release is carried out for one hour in 7 50 ml gastric fluid medium (0.1 M hydrochloric acid solution) at 37° C. This medium is thrown away after measurement of the 1 hour value and the release is then carried out in 7 50 ml of an 50 mM potassium dihydrogenphosphate buffer at pH 5 .8 at 3 7° C. for further 16 hours. 

The quantification of propiverine-hydrochloride or propiv› erine, respectively, in the release medium is carried out by means of an on-line coupled UV NIS-spectrophotometer. For the measurement the release medium is pumped at predefined periods from each release container through polypropylen filters via a 6-channel tube pump into the flow vessel of the UVNIS-spectrophotometer. The measurement of the extinc› tion is at 239 nm whereby the extinction at 247 nm is addi› tionally determined as the background. For calculation of the amount of propiverine-hydrochloride/propiverine the extinc› tion value at the background wavelength is subtracted from the extinction value at the measurement wavelength. 

The calculation of the release data is carried out in relation to one sample of a reference substance which is measured under the same conditions in the UV NIS-spectrometer. The amount of propiverine-hydrochloride or propiverine, respec› tively, which is released during the first hour in 0.1 M hydro› chloric acid is added to the further release values. 

The release data obtained are shown in Tables 1 and 2 as the mean values of a six fold determination. 

## Example 5 

