UV derivative spectrophotometric study of the photochemical degradation of nisoldipine

Zhou

et al. 2008

Biopharm & Drug Disp

The prototype 1,4-dihydropyridine (1,4-DHP) nifedipine, indicated for the management of hypertension and angina pectoris, has disadvantages including photodegradation and a short half-life. Several newer 1,4-DHPs, including m-nifedipine and its analogs at the C3, C5 position such as MN9201, MN9202 and MN9203, have been designed to offset these problems. The aim of this study was to investigate the pharmacokinetic characteristics of these derivatives to provide reference for their further evaluation and modification. Derivatives were intravenously bolus administered to beagle dogs. The drug concentration in the plasma was determined by the HPLC method. The pharmacokinetic parameters were calculated by the non-compartmental method. The analysis of variance (ANOVA) was used to compare the pharmacokinetic parameters of the derivatives. The results showed that the area under the curve from time zero to the last sampling time (AUC(0-t)) of m-nifedipine, MN9201, MN9202 and MN9203 was 45.1 +/- 13.6, 51.7 +/- 15.2, 70 +/- 16 and 62 +/- 12.4 micromol/l*min, respectively. The elimination half-life (t(1/2)) was 98 +/- 24, 129 +/- 55, 190 +/- 21 and 92 +/- 25 min, respectively. The t(1/2) of MN9202 was significantly longer than those of the others (p<0.05 or p<0.01). These results suggest that the length of the carbon chain at the C3 or C5 position in the derivatives had a marked effect on its metabolism, and M9202 is a promising new drug candidate worth further evaluation.

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of the analogs at C3 and C5 of m‐nifedipine in beagle dogs

Zhou

et al. 2008

Biopharm & Drug Disp

“…The test was monitored by UV derivative spectrophotometry [66]. In contrast, another work about photodegradation of this drug in solid state reported the appearance of the nitroso-phenyl-pyridine photoproduct under daylight while the formation of nitro-phenyl-pyridine under UV light.…”

Section: Nisoldipinementioning

confidence: 99%

Photodegradation of 1, 4-Dihydropyridine Antihypertensive Drugs: An Updated Review

Luca

Ioele

Spatari

et al. 2018

Int J Pharm Pharm Sci

ABSTRACT1, 4-dihydropyridine calcium channels blockers (DHPs) are the most commonly used antihypertensive drugs. Unfortunately, these compounds have a significant degradability to light. The oxidation to the pyridine derivative represents the first, and in many cases the only, step of the degradation mechanism. The photodegradation process causes the complete loss of pharmacological activity and may trigger the formation of single and superoxide oxygen species, potentially responsible for phototoxic reactions. Several analytical techniques have been proposed for DHP determination in the presence of their photoproducts. Nowadays, DHPs are all marketed in solid formulations, especially tablets, because photodegradation is particularly fast in solution. Various approaches aimed to protect molecular integrity and therapeutic activity of these drugs from the effects of light are currently studied. This review covers the studies over the last years about photodegradation of the DHPs and the approaches to obtain photostable formulations of these drugs.

Journal of Pharmaceutical Research

“…The mixture was then kept at ambient temperature for 24 h to attain equilibrium. The equilibrated sample was centrifuged (Remi RM 12C Centrifuge) at 4,000 rpm for 10 min to remove the undissolved drug which was then filtered off and the liquid was assayed through UV spectrophotometer 9,14 (Shimadzu UV-1700) at 298 nm. (Fig.1) …”

Section: Excipient Screening-saturation Solubility Studiesmentioning

confidence: 99%

A Self Emulsifying Drug Delivery System (SEDDS) for Nisoldipine: Characterization, Dissolution and Conversion into Solid Sedds

Khansili¹,

Bajpai²

2012

Poorly soluble drugs such as nisoldipine offer challenges in developing a drug product with adequate bioavailability. The objective of present study was to improve solubility and dissolution rate of nisoldipine by developing and characterizing self emulsifying drug delivery system (SEDDS) of nisoldipine. Solubility of nisoldipine was carried out in various oils, surfactants and co-surfactants. Six self emulsifying formulations were prepared using various proportions of oil, surfactants and co-surfactants in which solubility of nisoldipine was high. The stability studies after introduction of nisoldipine into different combinations provided the optimized liquid SEDDS comprising of capmul MCM EP, labrasol, tween 60 and polyethylene glycol 400, which was then evaluated for droplet size, percentage transmittance and coalescence studies. Liquid SEDDS was then converted into free flowing powder by adsorbing onto solid carriers. Solid state characterization of solid SEDDS was performed by scanning electron microscopy (SEM) and differential scanning calorimetric (DSC) measurements. The comparative dissolution studies with nisoldipine and SEDDS proved the efficiency of self emulsifying formulations in improving dissolution rate. The permeability studies as non everted sac method gave higher permeation rate for SEDDS. This solid SEDDS may provide a useful solid dosage form for oral poorly soluble drugs.