Dilution of semi-solid creams: influence of various production parameters on rheological properties and skin penetration.

UNLABELLED: In order to customise treatment for patients, topical formulations are often diluted with drug-free cream bases to adjust the drug dose and thereby the formulations' activity to the patients' needs. However, the process of dilution influences properties of the formulations. Stability can be reduced as well as the microbial stability and most importantly, efficacy and skin penetration behaviour can be severely and unpredictably changed. The present study investigates the effects of production parameters on creams, namely incorporation of an API (active pharmaceutical ingredients) into an OW cream with prior mixing with propylene glycol or without and subsequent automated or manual dilution of the resulting creams with three different cream bases. Effects were measured by influence on microscopic appearance, measurement of chemical stability, skin penetration and rheological behaviour. RESULT: suggest strong influence of the cream bases used for dilution of the formulations. Mixture of equal amounts of the employed OW and WO cream proved unfavourable due to inferior penetration behaviour and less appealing microscopic and macroscopic appearance. Prior mixing with PG was of negligible importance for the characteristics of the dilutions, however, the type of API and manner of dilution had an influence on the viscosity of the formulations.

Carcinoid tumors--somatostatine in the diagnosis and therapy.

BACKGROUND: Carcinoid tumors have a neuroendocrine origin and endocrine activity is typical for them. OBJECTIVES: The main objective of the present study was to determine differences in the levels of an endogenous somatostatin, a neuron specific enolase in serum and excretion of 5-HIAA in the urine in patients with carcinoid tumors and also to determine the changes of these parameters during the treatment with long acting somatostatin analogue--lanreotide. SUBJECTS AND METHODS: 30 pts with carcinoid tumors (20 pts with metastatic disease, 10 pts after resection of the primary tumor without known metastases at the time of the investigation) and 12 healthy probands were included in the study. Circadian rhythm of endogenous somatostatin in all groups was performed. Levels of neuron specific enolase in the serum and the excretion of 5-HIAA in the urine in pts with carcinoid tumors were done. The estimation of these parameters were repeated in the group of pts with advanced metastatic disease during the treatment with the lanreotide. RESULTS: We confirmed the existence of the circadian rhythm of endogenous somatostatin in all groups. Chronogram of somatostatin in pts without known metastases shows the same characteristics as the chronogram of healthy volunteers. The chronogram of pts with metastatic carcinoid disease shows a statistically significant differences in comparison with healthy volunteers--higher mesor and later acrophase of 24-hour rhythm (p < 0.05). During the therapy with lanreotide lower mesor was observed (p < 0.05). The amount of the 5-hydroxyindolacetate acid in urine in pts with metastatic carcinoid was statistically significant higher than in the pts without metastases (p < 0.001). During therapy with the lanreotide the decrease in the 5-HIAA in the urine (p < 0.05) was observed. Neuron specific enolase in the serum was higher in group with the metastatic disease (p < 0.001). CONCLUSION: Abnormalities in the somatostatin secretion and the concentration of the neuron specific enolase in serum are useful markers for the differential diagnosis and might distinguish the carcinoid patients with and without metastases. Urine excretion of 5-HIAA is a good marker of endocrine activity of the carcinoid tumor. (Fig. 4, Tab. 3, Ref. 22.)

[Diurnal rhythm of endogenous somatostatin in patients with carcinoid]. / Diurnálny rytmus endogénneho somatostatínu u pacientov s karcinoidom.

AIM OF THE STUDY: Was to investigate the differences of the circadian rhythm of the endogenous somatostatin in patients with carcinoid and in healthy probands. METHODS: The group of 30 patients (16 men/14 women) was divided onto two groups. The group M of 20 (12/8) pts with metastatic disease and group B of 10 pts without known metastases at the time of investigation. The control group A included by 12 healthy probands (7/5). Plasma levels of somatostatin were determined by radioimmunoassay. Fisher periodogram and Halberg's cosinor were used for statistical evaluation. RESULTS: We confirmed the 24-hour circadian rhythm of somatostatin in group A, B and M. Patients of the M group when compared with A and B groups had higher mesor and the later 24-hour acrophase (p < 0.05) and 12-hour acrophase (p < 0.05). Treatment with lanreotide led to the significant decrease of the somatostatin mesor (p < 0.05).