AimsThe aims of the study were to: (1) evaluate the gastrointestinal transit, release and absorption of budesonide from tablets with a new multimatrix formulation (M MX®) designed to release the drug throughout the whole colon, and (2) assess the influence of food on budesonide bioavailability. MethodsTwo phase I studies, each comprising 12 healthy males, were performed. Gastrointestinal transit of 153 Sm-labelled tablets containing 9 mg budesonide was evaluated by means of pharmaco-scintigraphy. The effect of food was tested by comparing plasma pharmacokinetics after intake of a high fat and high calorie breakfast with fasting controls. Results153 Sm-labelled tablets reached the ascending colon after a mean ± SD 9.8 ± 6.9 h. Initial tablet disintegration was observed in the ileum in 42% and the ascending and transverse colon in 33% of subjects. Ninety-six per cent of the dose was absorbed into the systemic circulation during passage through the whole colon including the sigmoid. Food significantly decreased C max values from 1429 ± 1014 to 1040 ± 601 pg mL − 1 ( P = 0.028) and AUC values from 14 814 ± 11 254 to 13 486 ± 9369 pg h − 1 mL − 1 ( P = 0.008). Mean residence time and t max increased by 12-29%. There was no drug accumulation after 1 week of once daily oral administration of budesomide. ConclusionsMMX®-budesonide tablets appear suitable for targeted colonic drug delivery. Transit parameters and low systemic bioavailability warrant further studies with the new formulation.

This pilot study supports the rationale for the use of topical antiandrogens in the treatment of acne vulgaris. CB-03-01 1% cream seems to fit with the profile of an ideal antiandrogen for topical use.

Theoretical calculations and NMR analyses were used in order to conformationally characterize the topical androgen cortexolone-17α-propionate (red shading) in comparison with other steroidal androgens and antiandrogens.

The aim of this study was to investigate the antiandrogenic activity of a new monoester of cortexolone, cortexolone 17alpha-propionate (CAS 19608-29-8, CB-03-01). Although the compound displayed a strong local antiandrogenic activity in hamster's flank organ test, it did not exhibit antiandrogenic activity in rats after subcutaneous injection, nor did it affect gonadotropins hypersecretion when injected to parabiotic rats. As topical antiandrogen, the steroid resulted about 4 times more active than progesterone (CAS 57-83-0) and, when compared to known antiandrogen standards, it was about 3 times more potent than flutamide (CAS 13311-84-7), about 2 times more effective than finasteride (CAS 98319-26-7) and approximately as active as cyproterone acetate (CAS 427-51-0). Its pharmacological activity seemed to be primarily related to its ability to antagonistically compete at androgen receptor level; nevertheless its primary pharmacological target needs to be further investigated. Its topical activity, along with the apparent absence of systemic effects, anticipates this compound to have the potential of representing a novel and safe therapeutic approach for androgen-dependent skin disorders.

SUMMARY BackgroundThe administration of parnaparin sodium as oral colon-release tablets (CB-01-05 MMX Ò ) has been proposed as a novel approach for the treat-