Transdermal application of H100 gel to the penile shaft in patients with Peyronie's disease infiltrates the tunica albuginea.

Treatment options for Peyronie's disease (PD) remain limited. Topical H100 gel, (Hybrid Medical, Edina, USA), which contains nicardipine, super oxide dismutase and emu oil showed safety and efficacy in a previous small double-blind placebo-controlled pilot study. The present study evaluates if topically applied H100 gel applied to the penile shaft infiltrates the tunica albuginea. Nicardipine is a key active ingredient in H100 and serves as a surrogate marker. Three men already scheduled to undergo a planned surgical procedure for PD applied commercially available H100 gel twice daily to the penile shaft for up to 30 days prior to the procedure. Tunica albuginea samples were obtained at surgery. Nicardipine evaluation was performed using isotope dilution technique via liquid-chromatograph-mass spectrometry (LCMS). All three patients tolerated H100 gel application without side effects. All three tunica albuginea specimens showed detectable nicardipine in the tunical tissue. Transdermal application of commercially available H100 gel is able to penetrate the tunica albuginea tissue and is detectable in men with acute and chronic PD. This finding may support the encouraging results found in the prior H100 pilot study.

Quantitative determination of amorphous nicardipine hydrochloride in long acting formula (NIC-LA) using light anhydrous silicic acid.

We investigated a method to quantitatively determine amorphous nicardipine hydrochloride (NIC) in the NIC-long acting formula (LA) model formulas prepared using NIC, light anhydrous silicic acid (LASA) and carboxymethylethylcellulose (CMEC). Consequently, since the quantity of total NIC in the formula can be determined by means of HPLC and crystal NIC can be determined by the differential scanning calorimetry (DSC) method because the heat of fusion (85.08 J/g) of NIC is constant and unaffected by excipients, we developed the HPLC-DSC method by which the quantity of amorphous NIC is calculated as the difference between the quantity of total NIC determined by HPLC and the quantity of crystal NIC determined by DSC. This practical HPLC-DSC method was confirmed to have good accuracy and reproducibility.

Photostability studies on nicardipine-cyclodextrin complexes by capillary electrophoresis.

Nicardipine (NC)-cyclodextrin solid systems were prepared in equimolar ratios and their photostability in aqueous solution under exposure to UV(A)-UV(B) radiations was evaluated. The photodegradation process was monitored by a capillary electrophoresis (CE) method able to provide the enantioresolution of the rac-nicardipine. Enantioresolution was achieved using the mixture 3.0% sulfate-beta-cyclodextrin (SbetaCD) and 2.0% heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMbetaCD) as chiral selector in 20mM triethanolammonium phosphate solution (pH 3.0). The photostability studies were carried out on inclusion complexes of rac-nicardipine with alpha-cyclodextrin (alphaCD), beta-cyclodextrin (betaCD), gamma-cyclodextrin (gammaCD), hydroxypropyl-alpha-cyclodextrin (HPalphaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), hydroxypropyl-gamma-cyclodextrin (HPgammaCD), (2-hydroxyethyl)-beta-cyclodextrin (HEbetaCD) and methyl-beta-cyclodextrin (MbetaCD). A photoprotective effect was observed by betaCD, HPalphaCD, HEbetaCD, whereas gammaCD, MbetaCD, HPbetaCD and HPgammaCD did not affect the nicardipine photostability. Conversely, alphaCD was found to favour the drug photodegradation. Evidences for CDs-mediated stereoselective photodegradation of rac-nicardipine were observed only for the beta-CD complex. In this case, two distinct photodegradation profiles, with two different kinetic constants (k), were observed for the nicardipine enantiomers.

Interaction of Ginkgo biloba extract (GBE) with hypotensive agent, nicardipine, in rats.

The effect of Ginkgo biloba extract (GBE, 0.5%) orally administered for 2 weeks on the antihypertensive action of oral nicardipine was examined in Wistar rats. GBE significantly increased hepatic P-450 content and reduced the hypotensive effect of nicardipine. GBE administration resulted in a significant decrease in maximal nicardipine plasma concentration (Cmax) and the 23-hour area under the curve (AUC0-23). Thus, it is suggested that GBE attenuated the therapeutic potency of nicardipine, probably secondary to increased hepatic drug metabolism.

Formulation and evaluation of sustained release floating capsules of nicardipine hydrochloride.

Nicardipine hydrochloride, a calcium channel blocker with significant vasodilating and antihypertensive activities, was formulated in this work as sustained release floating capsules. A hydrocolloid of high viscosity grade was used for the floating systems. The inclusion of sodium bicarbonate to allow evolution of CO2 to aid buoyancy was studied. Polymers that retard drug release were included as coprecipitates with the drug and/or as additives in the formulated capsules. Both simple powder mixing of the ingredients and granule preparation via wet granulation were used. Seven capsule formulae were prepared. The prepared capsules were evaluated in vitro by testing drug dissolution, floating time and the kinetics of drug release. In vitro evaluation of a commercially available conventional 20 mg capsule of nicardipine hydrochloride, "Micard", was carried out for comparison. The hydrocolloid used succeeded in effecting capsule buoyancy. Floating time increased with increasing the proportion of the hydrocolloid. Inclusion of sodium bicarbonate increased buoyancy. All of the seven floating capsule formulae prepared proved efficient in controlling drug release. The sustained release floating capsule formulation of choice was evaluated in vivo in comparison to "Micard" capsules using rabbits. Reversed phase HPLC with UV detection was used for drug determination in rabbit plasma. Plasma concentration time curves revealed a longer drug duration for administration in the sustained release formula than the conventional "Micard" capsule being 16 h in the former versus 8 h for the latter.

Intrathecal administration of nicardipine hydrochloride to prevent vasospasm in patients with subarachnoid hemorrhage.

OBJECT: To evaluate the prophylactic effect of repeated intrathecal administration of nicardipine associated with hypertensive hypervolemic hemodilution therapy (triple H) and sodium correction, we analyzed a consecutive series of 177 patients with subarachnoid hemorrhage. METHODS: All patients received aneurysmal clipping and placement of cisternal drainage within 48 hours of the onset. Intrathecal administration of 4 mg of nicardipine was performed every 12 h. Nicardipine concentrations in the cerebrospinal fluid (CSF) and blood before and after its administration were analyzed. Angiographic vasospasm (aVS), symptomatic VS (sVS), and clinical outcome 6 months after onset were also evaluated. RESULTS: Nicardipine concentration in CSF on day 9 was 231.44 +/- 51.51 ng/ml (mean +/- SD), and that of blood was 21.05 +/- 15.57 ng/ml. Twenty patients (11.3%) showed aVS, and ten of those (5.7%) showed sVS (six were transient and four were permanent). Those with good outcome (assessed as good recovery and moderately disabled) 6 months after onset were 89.2% of the total. The number of patients requiring a shunt operation was 33 of 177 (18.6%), and 11 patients presented intracranial infection. CONCLUSIONS: These results suggest that our strategy may well prevent VS. However, hydrocephalus and infection may be serious disadvantages that should be resolved.

Resolution of newly synthesized racemic dihydropyridines with different chiral selectors by means of capillary electrophoresis.

The racemates of newly synthesized 4-aryl-1,4-dihydropyridine derivatives attracting interest in the treatment of coronary insufficience were resolved via the formation of diastereomeric salts. In order to check the quality of the preparative resolution, capillary electrophoresis using neutral cyclodextrins (CDs) was developed. In particular, the alpha-CD was found to be a powerful discriminator of the enantiomers. Additionally, taking amlodipine and nicardipine into consideration, a mechanism of the chiral recognition with alpha-CD could be proposed.

Adsorptive stripping voltammetry of nicardipine at a HMDE; determination of trace levels nicardipine in blood and urine.

The redox behaviour of nicardipine, a 1,4-dihydropyridine calcium antagonist, has been studied in different media on mercury, glassy carbon, gold and platinum electrodes using various voltammetric techniques. A highly sensitive adsorptive stripping voltammetric method for the determination of nicardipine based on adsorption of the drug onto mercury, followed by differential pulse voltammetric determination of the surface species, is described. All factors (pH, supporting electrolyte, accumulation potential and time, etc.) influencing adsorption as well as voltammetric response are discussed. The application of adsorptive stripping voltammetry at the hanging mercury drop electrode (HMDE) to the determination of trace levels of nicardipine in human urine and blood is illustrated, without an extraction procedure being necessary prior to the voltammetric measurement. A limit of detection of 4.8 ng per ml urine and 34 ng per ml blood is found with a mean recovery of nicardipine in urine and blood of 97%. The mean relative error does not exceed 6.5%.

The compatibility of nicardipine hydrochloride injection with various ICU medications during simulated Y-site injection.

Physical incompatibility studies between an intravenous calcium channel antagonist, nicardipine hydrochloride, and potentially coadministerable ICU medications have been performed. Forty-one medications and four solutions were evaluated. The medications were anesthetic/narcotics, antibiotics, an anticoagulant, a bronchodilator, electrolyte solutions, fluids, H2 receptor blocking agents, steroids and vasoactive agents. Of the forty-five substances, three showed evidence of physical incompatibility as manifested by turbidity, precipitation, or color change. All three were antibiotics. These were ampicillin, ampicillin/sulbactam sodium, and cefoperazone. We conclude that until bioavailability studies are performed these three antibiotics should not be coadministered with nicardipine HCl.

Experience with routine applications of liquid chromatography-mass spectrometry in the pharmaceutical industry.

The combination of liquid chromatography and mass spectrometry (LC-MS) has been established to complement gas chromatography (GC)-MS in the analysis of non-volatile and labile drugs in complex materials. The possibilities of LC-MS in the pharmaceutical industry for the analysis of drug substances and dosage forms, metabolism studies and the elucidation of the structures of materials of biological origin are discussed. Instrumental requirements, limitations and applications of LC-MS are considered and experiences with LC-MS in routine applications are reported. Preliminary results obtained with thermospray LC-MS are compared with those using a direct liquid inlet interface.