Nifedipine Capsules Research Articles

Design and characterisation of an amorphous formulation of nifedipine for the treatment of autonomic dysreflexia.

Current treatment for autonomic dysreflexia (AD) involves rupturing a liquid-filled soft capsule of nifedipine to aid rapid drug release and absorption, however, this application is not covered under the manufacturer's license. The objective of the current work was to design a rapidly dissolving solid dosage formulation for the treatment of AD as an alternative to the off-license "bite and swallow" use of currently available commercial products. Amorphous solid dispersions (ASDs) of nifedipine were prepared by spray-drying using three different polymers: hydroxypropyl methyl cellulose (HPMC), polyvinyl pyrrolidone (PVP) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus), at a 15% w/w drug loading and were formulated and compressed into tablets. Dissolution testing was performed in the paddle dissolution apparatus using either a monophasic or biphasic medium. The PVP-nifedipine ASD tablets exhibited rapid dissolution, with 35% of the total nifedipine dose dissolving within 15 min in the monophasic dissolution medium. The HPMC-nifedipine ASD exhibited a very slow dissolution, while the Solupus-nifedipine system exhibited no nifedipine release over 120 min. When tested in the biphasic dissolution medium, the PVP-nifedipine ASD tablets exhibited a release profile comparable to that of the pre-split/ruptured nifedipine soft capsule product. This study demonstrates that a nifedipine-PVP ASD is a promising formulation strategy in the treatment of AD.

Evaluation of physicochemical properties and dissolution studies on quality control of low water solubility drugs (raw materials and pharmaceutical formulations)

The purpose of this study was to evaluate physicochemical properties and dissolution studies of furosemide (FUR), hydrochlorothiazide (HCTZ) and nifedipine (NIF), low water solubility drugs, in raw materials and pharmaceutical formulations. Surface and physicochemical characterization techniques -scanning electronic microscopy (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and infrared (IR) spectrometry- as well as physical and physicochemical tests on tablets and capsules were applied as supporting information on drug quality control. Simple, rapid, and efficient UV-Vis methods were developed and validated for the determination of FUR, HCTZ and NIF samples. SEM exhibited considerable differences in the crystal morphological structures. Among the drugs studied, except for furosemide, more than one polymorph was present in the samples. Drug release profiles were satisfactory for all products. FUR and HCTZ tablets exhibited similar dissolution profiles, with very rapid release to the pharmaceutical specialties (reference, similar and generic). For HCTZ tablets, the similar drug (f2= 48.74) is not equivalent to the reference drug. NIF capsules (reference and compounded) showed a release ≥80% of stated on product labels, in 10 minutes. The results obtained in this study suggest that the quality parameters and drug dissolution profiles may have been influenced by the morphology and size of the crystals, excipients, and technological processes.

A COMPARATIVE STUDY BETWEEN THE EFFICACY OF NIFEDIPINE AND HYDRALAZINE IN SEVER PREECLAMPSIA IN THE THIRD TRIMESTER OF PREGNANCY AND COMPARISON THE PERINATAL OUTCOME IN SULAIMANI MATERNITY TEACHING HOSPITAL

Background Preeclampsia is an idiopathic disorder of pregnancy characterized by proteinuric hypertension; hydralazine is an arterial vasodilator antihypertensive drug. Nifedipine is a calcium channel blocker antihypertensive drug. Objective To compare the effect of intravenous hydralazine and oral immediate release nifedipine capsule in patients with severe preeclampsia in their 3rd trimester of pregnancy and compare the early perinatal outcome. Material and Methods A prospective cohort study set at Sulaimani Maternity Teaching Hospital, Sulaimani, Iraq, throughout period of January first 2015 to September first 2015. The study includes 50 patients diagnosed with sever preeclampsia (blood pressure ≥ 160/110 mmHg and > 1 gram proteinuria) in the third trimester of pregnancy, who admitted to Emergency Department of Sulaimani Maternity Teaching Hospital from January, first 2015 to September, first 2015. Patients had been divided into two groups, the first 25 patients had received hydralazine and the second 25 patients received nifedipine. The blood pressure and fetal heart rate recorded before and after the treatment, the target blood pressure: Systolic blood pressure < 160 mmHg and diastolic blood pressure < 110 mmHg. Results Both drugs were ultimately effective in reaching the therapeutic goal because there were no failures requiring crossover in either study group. Patients received intravenous hydralazine achieved the therapeutic blood pressure more rapidly in (38.0±14.0) minutes (mean±SD) as compared with (51.3±23.9) minutes who received oral immediate release nifedipine. P=0.05. Both drugs had no effect on fetal heart rate but they had many maternal side effects especially with hydralazine which associated with more palpitation than nifedipine (12% versus 8%). In mode of delivery, 72% of women from hydralazine group and 52% of women from nifedipine group their pregnancies are terminated by caesarean section, while 36% of women from nifedipine group and 20% of women from hydralazine group were delivered vaginally. Conclusion Both drugs are efficient in controlling the blood pressure in sever preeclampsia and no significant difference in perinatal outcome. Nifedipine needed longer period but less number of doses to reach the goal blood pressure. Because the nifedipine’s oral bioavailability and less frequent side effects, it more preferable anti-hypertensive therapy in emergency cases compared to the hydralazine.

In-situ freeze-drying - forming amorphous solids directly within capsules: An investigation of dissolution enhancement for a poorly soluble drug

Conversion into the amorphous form enhances the dissolution of poorly soluble drugs, however the barrier to market for medicines containing an amorphous drug is poor stability. The aim was to produce the amorphous form of a drug within a capsule, without thermal or mechanical stress during manufacture. To facilitate this aim, the mechanism for drug-polymer interaction was explored. Nifedipine and polyvinylpyrrolidone were dissolved in tert-butanol at different drug/polymer ratios. These solutions were dispensed into gelatin capsules and freeze-dried. Differential scanning calorimetry (DSC) & novel FT-IR analysis based on peak symmetry measurements confirmed the absence of crystallinity when polyvinylpyrrolidone exceeded 50%w/w. Capsules containing 10 mg of nifedipine were amorphous and stable for over 3 months at ≈40 °C. Evidence of hydrogen bonding between the N-H group of nifedipine and the C=O group of PVP was observed and this interaction inhibited nifedipine crystallisation. PVP’s high affinity for water and the nifedipine-polymer interaction lead to a significant dissolution rate enhancement. The freeze-dried capsule, 10%w/w nifedipine/PVP, had the highest dissolution rate constant of 0.37 ± 0.05 min−1, and the lowest time to achieve 50% dissolution or t1/2 of 1.88 ± 0.05 min. This formulation reached 80% dissolved in less than 6 min whereas the equivalent marketed liquid filled nifedipine capsule took 3 times longer to reach 80% dissolution.

Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis

In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium. The dissolution profiles of two nifedipine capsules (poorly soluble compound), under conditions mimicking the intake of the capsules with i. water, ii. orange juice and iii. an alcoholic drink (orange juice and ethanol) were analysed using multiple linear regression (MLR). Optimised dissolution set-ups, generated based on the mathematical model obtained via MLR, were used to build predicted in vitro-in vivo correlations (IVIVC). IVIVC could be achieved using physiologically relevant in vitro conditions mimicking the intake of the capsules with an alcoholic drink (orange juice and ethanol). The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions.

An in vitro–in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics

The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro–in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages.

Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review.

BackgroundPregnant and postpartum women with severe hypertension are at increased risk of stroke and require blood pressure (BP) reduction. Parenteral antihypertensives have been most commonly studied, but oral agents would be ideal for use in busy and resource-constrained settings.ObjectivesTo review systematically, the effectiveness of oral antihypertensive agents for treatment of severe pregnancy/postpartum hypertension.Search strategyA systematic search of MEDLINE, EMBASE and the Cochrane Library was performed.Selection criteriaRandomised controlled trials in pregnancy and postpartum with at least one arm consisting of a single oral antihypertensive agent to treat systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 110 mmHg.Data collection and analysisCochrane RevMan 5.1 was used to calculate relative risk (RR) and weighted mean difference by random effects.Main resultsWe identified 15 randomised controlled trials (915 women) in pregnancy and one postpartum trial. Most trials in pregnancy compared oral/sublingual nifedipine capsules (8–10 mg) with another agent, usually parenteral hydralazine or labetalol. Nifedipine achieved treatment success in most women, similar to hydralazine (84% with nifedipine; relative risk [RR] 1.07, 95% confidence interval [95% CI] 0.98–1.17) or labetalol (100% with nifedipine; RR 1.02, 95% CI 0.95–1.09). Less than 2% of women treated with nifedipine experienced hypotension. There were no differences in adverse maternal or fetal outcomes. Target BP was achieved ∼ 50% of the time with oral labetalol (100 mg) or methyldopa (250 mg) (47% labetelol versus 56% methyldopa; RR 0.85 95% CI 0.54–1.33).ConclusionsOral nifedipine, and possibly labetalol and methyldopa, are suitable options for treatment of severe hypertension in pregnancy/postpartum.

Prevention and treatment of postpartum hypertension

Postpartum blood pressure (BP) is highest three to six days after birth when most women have been discharged home. A significant rise in BP may be dangerous (e.g., can lead to stroke), but there is little information about how to prevent or treat postpartum hypertension. To assess the relative benefits and risks of interventions to: (1) prevent postpartum hypertension, by assessing whether 'routine' postpartum medical therapy is better than placebo/no treatment; and (2) treat postpartum hypertension, by assessing whether (i) one antihypertensive therapy is better than placebo/no therapy for mild-moderate postpartum hypertension; and (ii) one antihypertensive agent offers advantages over another for mild-moderate or severe postpartum hypertension. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2013), bibliographies of retrieved papers, and personal files. For women with antenatal hypertension, trials comparing a medical intervention with placebo/no therapy. For women with postpartum hypertension, trials comparing one antihypertensive with either another or placebo/no therapy. We extracted the data independently and were not blinded to trial characteristics or outcomes. We contacted authors for missing data when possible. Nine trials are included. Four trials (358 women) compared furosemide, nifedipine capsules, or L-arginine with placebo/no therapy. For women with antenatal pre-eclampsia, postnatal furosemide is associated with a strong trend towards reduced use of antihypertensive therapy in hospital. For treatment of mild-moderate postpartum hypertension, three trials (189 women) compared timolol, oral hydralazine, or oral nifedipine with methyldopa. Use of additional antihypertensive therapy did not differ between groups (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.20 to 4.20; three trials), but the trials were not consistent in their effects. The drugs were well tolerated.For treatment of severe postpartum hypertension, two trials (120 women) compared intravenous hydralazine with either sublingual nifedipine or intravenous labetalol. There were no maternal deaths or hypotension. Use of additional antihypertensive therapy did not differ between groups (RR 0.58, 95% CI 0.04 to 9.07; two trials), but the trials were not consistent in their effects. For women with pre-eclampsia, postnatal furosemide may decrease the need for postnatal antihypertensive therapy in hospital, but more data are needed on substantive outcomes before this practice can be recommended. There are no reliable data to guide management of women who are hypertensive postpartum. Any antihypertensive agent used should be based on a clinician's familiarity with the drug. Future studies should include data on postpartum analgesics, severe maternal hypertension, breastfeeding, hospital length of stay, and maternal satisfaction with care.

Psychosomatic Component

Long-term therapy with immediate-release nifedipine is rightly considered to be obsolete. However, the prescription observed by the authors, as a single administration, shows that the reason for the prescription was not long-term treatment. The authors' recommendation of supervising and monitoring patients in intensive care rather than issuing a prescription is often pointless, as primary care experiences have shown. Of course there are extreme hypertensive crises that require supervision and monitoring in intensive care, but this is not the most common course. Hypertensive crises are known to have a psychosomatic component. The patients are agitated; they have cardiac palpitations; on measuring their own blood pressure they find an increased value; and they become anxious. Their blood pressure rises further, and their anxiety turns into panic. Because of this feedback effect patients often develop so-called cardiophobia. The result: anxious self-monitoring with rising blood pressure, increased overall medication, and more frequent spikes in blood pressure. Frequent admission to hospital would increase the psychosomatic pathological process. Hypertensive crises can of course occasionally be resolved by the family physician, but the significance of the required medical consultation also increases the pathogenic feedback effect. On the other hand: if the effectiveness of a transmucosal-resorption nifedipine capsule for hypertensive crisis has been demonstrated by the doctor, then having a small quantity of this “rescue medication” in the cupboard has a calming effect on the patient. Experience has shown that utilization is low. Just the awareness that self-help is available reduces the anxiety, breaks the vicious cycle, and reduces drug costs, medical consultations, and admissions to hospital.

PP088. Oral antihypertensive therapy for severe hypertension in pregnancy

The hypertensive disorders of pregnancy are among the leading causes of maternal mortality and morbidity. The vast majority occurs in low and middle income countries. It is widely accepted that women with severe hypertension are at increased risk of stroke and benefit from blood pressure (BP) reduction. Although traditionally, parenteral antihypertensive agents have been studied for treatment of severe hypertension in pregnancy, oral agents would be ideal for use in the community and in under-resourced settings. To review the published evidence for the effectiveness of oral antihypertensive therapy for severe hypertension in pregnancy. The following databases were searched (to May/11) for randomised controlled trials (RCT) of oral antihypertensive therapy for severe hypertension in pregnancy: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews. Inclusion criteria were: severe hypertension [an inclusion criterion or average enrollment BP of: systolic BP ⩾160mmHg and/or diastolic BP ⩾110mmHg), use of oral or sublingual antihypertensive therapy in at least one of the treatment arms, and at least one relevant measure of maternal or perinatal outcome within a week of administration. Data were abstracted independently by two reviewers and discrepancies resolved by consensus. The Cochrane Revman 5.1 software was used for statistical analysis according to standardised methodology. We identified 14 eligible trials (796 women). Most compared oral/sublingual (SL) nifedipine 5-10mg (10 trials, 606 women, 8/10 trials specified capsule preparation), with either: intravenous (iv) hydralazine 5-20mg (6 trials, 282 women), oral nifedipine 10mg PA tablets (1 trial), oral prazosin 1mg (1 trial), iv labetalol (1 trial), or iv/intramuscular (im) chlorpromazine 12.5 (1 trial). Three trials (154 women) compared oral methyldopa (250-500mg initially) with either oral labetalol (100mg), atenolol (50-200mg) or kentanserin (80-120mg) (1 trial each). One trial (36 women) compared SL isosorbide 1.25mg with iv magnesium sulphate (4g iv then 1g/hr). No trials were identified that compared oral labetalol with either parenteral hydralazine or oral nifedipine. Nifedipine compared favourably with parenteral hydralazine with no differences seen in BP control or maternal or perinatal outcomes. Heterogeneity between trial results was seen within the oral/SL nifedipine vs. iv hydralazine subgroup in which one trial evaluated treatment success and side effects over 20min, and found that nifedipine was associated with relatively lower success and fewer side effects. The incidence of maternal hypotension in the nifedipine capsule arms of these trials was low (1/102, 3 trials), but hypotension was common in both arms of a trial of nifedipine 10mg capsule vs. 10mg PA tablet trial (i.e., 11/31 vs. 3/33, risk difference 26%, 95% CI7% to 46%). Given the available RCT data on which to base oral antihypertensive treatment of severe hypertension in pregnancy, the choice of antihypertensive agent may need to be driven by the availability of the drug, setting in which it is to be administered, and by whom. For facility use, the evidence supports oral nifedipine capsules.

Attenuation of the Pressor Response to Tracheal Intubation in Severe Preeclampsia: Relative Efficacies of Nitroglycerine Infusion, Sublingual Nifedipine, and Intravenous Hydralazine

Background: The pressor response to laryngoscopy is known to be exaggerated in patients with severe preeclampsia. Objectives: The aim of the present study was to compare the efficacies of continuous intravenous (IV) infusion of nitroglycerine, IV hydralazine, or sublingual nifedipine in modifying cardiovascular responses to endotracheal intubation, in women with severe preeclampsia undergoing cesarean delivery under general anesthesia. Patients and Methods: A total of 120 patients undergoing cesarean delivery were randomly divided into 3 groups, each receiving one of the following drugs before intubation: 5 µg/min nitroglycerine administered by continuous IV infusion (Group NTG, n = 40); a 10-mg capsule of nifedipine deposited sublingually (Group NIF, n = 40); or 5–10 mg hydralazine intravenously (Group H, n = 40). Heart rate (HR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were simultaneously recorded in the mother at pre-induction, pre-intubation, and at 1, 3, 5, and 10 min after intubation. Results: In contrast to those in group NIF and group H, the patients in group NTG showed no significant increases in HR, SAP, DAP, or MAP after intubation, compared to baseline. The incidence of hypotension was significantly greater in group NIF than in group H or group NTG [15 (37. 5%) vs. 8 (20%) vs. 5 (12. 5%) respectively, P = 0. 025]. Conclusions: In patients with severe preeclampsia undergoing cesarean delivery, a continuous IV infusion of nitroglycerine was able to attenuate the cardiovascular response to intubation to a greater extent than the use of sublingual nifedipine or IV hydralazine, without significant adverse effects on the newborn.

How to manage hypertension in pregnancy effectively.

The hypertensive disorders of pregnancy (HDP) are a leading cause of maternal mortality and morbidity in both well and under-resourced settings. Maternal, fetal, and neonatal complications of the HDP are concentrated among, but not limited to, women with pre-eclampsia. Pre-eclampsia is a systemic disorder of endothelial cell dysfunction and as such, blood pressure (BP) treatment is but one aspect of its management. The most appropriate BP threshold and goal of antihypertensive treatment are controversial. Variation between international guidelines has more to do with differences in opinion rather than differences in published data. For women with severe hypertension [defined as a sustained systolic BP (sBP) of ≥160 mmHg and/or a diastolic BP (dBP) of ≥110 mmHg], there is consensus that antihypertensive therapy should be given to lower the maternal risk of central nervous system complications. The bulk of the evidence relates to parenteral hydralazine and labetalol, or to oral calcium channel blockers such as nifedipine capsules. There is, however, no consensus regarding management of non-severe hypertension (defined as a sBP of 140-159 mmHg or a dBP of 90-109 mmHg), because the relevant randomized trials have been underpowered to define the maternal and perinatal benefits and risks. Although antihypertensive therapy may decrease the occurrence of BP values of 160-170/100-110 mmHg, therapy may also impair fetal growth. The potential benefits and risks do not seem to be associated with any particular drug or drug class. Oral labetalol and methyldopa are used most commonly, but many different β-adrenoceptor blockers and calcium channel blockers have been studied in clinical trials.

Accumulation of nifedipine after multiple doses.

The single and multiple dose pharmacokinetics of oral nifedipine capsules, 10 mg, have been examined in five patients with peripheral vasospasm. After a single dose, nifedipine was rapidly absorbed in three and slowly absorbed in two patients. Mean bioavailability parameters included a tmax of 2.9 h, a Cmax of 33.3 ng ml-1 and a AUC0-8 h of 113.3 ng h ml-1. After multiple dosing with either 10 or 20 mg every 8 h for 10 days the mean tmax at steady state was 2.1 h while the mean dose-corrected (to 10 mg) Cmax and AUC0-8 h were 51.9 ng ml-1 and 146.9 ng h ml-1, respectively. The mean elimination rate constant was 0.173 h-1 after both single and multiple doses. The mean extent of accumulation of nifedipine, defined as the ratio of AUC0-8 h (steady state)/AUC0-8 h (single dose), was 1.3; we concluded that nifedipine accumulates in the body when it is administered every 8 h. This should be taken into account when predicting steady state serum concentrations and haemodynamic effects of nifedipine from single dose kinetic data.

Bioequivalence of nifedipine softgel and capsule in healthy Chinese volunteers by liquid chromatography–mass spectrometry

The study aimed to compare and evaluate the bioequivalence of Calcigard-10 softgel and Adalat 10 capsule in healthy Chinese volunteers in a randomized, two-way cross over study design with a washout period of 7 days. A sensitive and reproducible electro-spray ionization liquid chromatography-mass spectrometry (ESI-LCMS) assay was developed and validated to determine nifedipine in human plasma using nitrendipine as internal standard. Nifedipine and nitrendipine were extracted from plasma using liquid-liquid extraction with methylene chloride as extraction solvent. The separation was performed by a Diamonsil ODS column (150 x 4.6 mm, 5 microm). The mobile phase was consisted of acetonitrile-5 mM ammonium acetate (52:48, v/v), delivered at flow rate of 1 mL/min. The 90% confidence intervals for the ratio values of logarithmic transformed Cmax and AUC were calculated to evaluate the bioequivalence of two preparations. The values of Cmax (92.3-112.7%), AUC0-t (84.5-95.1%) and AUC0-inf (84.4-95.5%) are within the interval criterion of 70-143% for Cmax and 80-125% for AUC. The Calcigard-10 softgel and Adalat 10 capsule are bioequivalent.

Cold stimulus fingertip lacticemy test an effective method to monitor acute therapeutic intervention on primary Raynaud's phenomenon and systemic sclerosis

The recently developed cold stimulus fingertip lacticemy test (CS-FTL) provides biochemical assessment of peripheral perfusion in patients with Raynaud's phenomenon (RP). We evaluated how the CS-FTL test can assess the acute effect of nifedipine in microvascular dynamics on primary RP and RP secondary to SSc. A double-blinded controlled trial with crossover design was performed in 20 primary RP and 20 SSc patients. Patients received one single sublingual placebo or 10 mg nifedipine capsule, with crossover after a 15-day washout period. FTL was determined in resting conditions (pre-CS-FTL) and 10 min after CS (post-CS-FTL), before and 1 h after drug administration. Percent variation in post- vs pre-CS-FTL was expressed as deltaCS-FTL. Before intervention, CS induced FTL decrease in primary RP (deltaCS-FTL = -21.3 +/- 13.0%) and FTL increase in SSc patients (deltaCS-FTL = +24.5 +/- 21.2%). Placebo had no effect on pre-CS-FTL, post-CS-FTL and deltaCS-FTL in primary RP and SSc. Nifedipine induced a significant decrease in pre-CS-FTL (1.94 +/- 0.45 vs 1.57 +/- 0.41 mg/dl; P = 0.005) and post-CS-FTL (1.53 +/- 0.35 vs 1.32 +/- 0.37 mg/dl; P = 0.004) in primary RP and a significant decrease in post-CS-FTL (3.18 +/- 1.43 vs 2.56 +/- 1.30 mg/dl; P = 0.028) and deltaCS-FTL (+15.9 +/- 24.7% vs -12.9 +/- 16.6%; P = 0.001) in SSc. The CS-FTL test was able to demonstrate and quantify a dual effect of nifedipine on the biochemical dimension of peripheral perfusion in primary RP and in SSc patients in which there was a significant improvement in tissue perfusion in resting conditions and after exposure to a CS. The CS-FTL test will enrich the armamentarium for investigation and clinical evaluation of conditions associated with RP.

Nifedipine Pharmacokinetics and Plasma Levels in the Management of Preterm Labor

The aim of this study was to determine if the dose regimen of nifedipine used for tocolysis was effective to achieve uterine quietness, and at which plasma concentration levels this tocolysis was achieved to optimize our dose regimen of nifedipine. In women with preterm labor, nifedipine was administered orally to achieve uterine quietness to prevent preterm birth. Patients (n = 5) were administered 10 mg nifedipine capsules (Adalat capsules, Bayer AG) orally every 15 minutes up to 40 mg in the first hour, and were subsequently given 1 tablet of 20 mg nifedipine slow release (Adalat retard, Bayer AG) t = 90 min. Plasma levels of nifedipine were measured at regular intervals during the first 4 hours after starting tocolysis. In all 5 patients tocolysis was achieved with nifedipine. Peak plasma concentration of nifedipine was 127.2 +/- 44 ng/mL at 1.2 +/- 0.1 hours. Mean plasma concentrations of nifedipine was 67.4 +/- 28.4 ng/mL. In all patients, tocolysis was achieved during the 4 hours of blood sampling. There were no adverse hemodynamic side effects seen before and after starting tocolysis with nifedipine. Initial dose regimen of 4 times 10 mg nifedipine capsule orally in the first hour, followed by 20 mg slow release nifedipine at t = 90 min is effective in achieving tocolysis in women with preterm labor. In steady state, the mean nifedipine plasma concentration to achieve tocolysis is about the half of that measured after initial tocolysis. Use of nifedipine for preterm labor was not associated with any adverse hemodynamic side effects.

Nifedipine capsules may provide a viable alternative to oral powders for paediatric patients

To compare content uniformities between different sizes of extemporaneously compounded nifedipine oral powders and capsules, in order to find out if capsules could be used instead of oral powders as paediatric medications. Actual content and content uniformity of extemporaneously compounded 1-mg nifedipine oral powders and capsules were evaluated by a high performance liquid chromatographic assay. Capsules and powders were prepared by triturating 10-mg nifedipine tablets with different amounts of lactose or microcrystalline cellulose with a mortar and pestle using a standard geometric dilution technique. Oral powders were weighed individually and capsules were filled by a hand-operated capsule-filling machine. Four different sizes of powders (500, 300, 100 and 50 mg) and three different sizes of capsules (numbers 1, 3 and 4) were prepared. Ten oral powders and 10 capsules from each batch were randomly selected and individually assayed for nifedipine amount. The extemporaneously prepared nifedipine oral powders and capsules were within acceptable limits for content uniformity, as defined by the European Pharmacopoeia, but the results indicate that the loss of nifedipine during the preparation process may be considerable for both preparations. The concentration on nifedipine decreased while the total mass of the oral powder decreased. These results demonstrate that nifedipine oral powders can be replaced by capsules, whose contents are emptied for use, in paediatric medications. Compounding small capsules, such as size number 3 or 4, is acceptable when considering the average drug content. The total weight of the oral powder should be at least 300 mg. The preparation of nifedipine in all studied capsule sizes was safe with either lactose monohydrate or microcrystalline cellulose as excipients. Thus, emptied capsules seem to be a good choice for delivering a paediatric medication. The loss of nifedipine was considerable in oral powders with low total weight.

Retention of Extended Release Nifedipine Capsules in a Patient with Enteric Stricture Causing Recurrent Small Bowel Obstruction

Medication bezoars from extended release medication have been reported in the literature. This has become an increasing phenomenon with the popularity of extended release formulations, which aim to increase therapeutic compliance. We report on a patient who experienced recurrent bouts of small bowel obstruction, necessitating surgical exploration.

Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms

To develop a model based on mean residence time for better understanding the effect of grapefruit juice on the metabolism of nifedipine (NIF). Sixteen healthy volunteers from an urban population were included. For each trial, the subjects drank water, fresh grapefruit juice or bottled grapefruit juice. Thirty minutes later, the subjects took a 10 mg capsule of NIF, orally. Plasma concentration of NIF was measured and the kinetic parameters were calculated with a non-compartmental model. Grapefruit juice increased the bioavailability of NIF, but did not significantly reduce the drug's metabolism as shown by the approximately constant metabolite to parent drug AUC ratio (P = 0.948). There was no significant increase in the amount of non-metabolized drug absorbed during first-pass: 0.12 and 0.16 (P = 0.470) without and with grapefruit juices respectively. There was an increase in the relative bioavailability (P = 0.039) and the apparent volume of distribution (Vdm) (P = 0.025) of dehydronifedipine with grapefruit co-administration. A second peak was also observed in the NIF plasma-concentration profile when the drug is co-administered with grapefruit juice. Therefore, the most likely explanation for the double peak phenomenon is a delay in gastric emptying (+32 min with grapefruit juice) caused by the pH of grapefruit juice. This study shows that grapefruit juice interferes with the metabolism of NIF by inhibiting NIF metabolism and slowing down the rate of gastric emptying. This study also confirms that the metabolic inhibition is not a first pass effect, but is a secondary oxidative step.

Nifedipine for Severe Hypertension in Pregnancy: Emotion or Evidence?

A meta-analysis of randomized controlled trials suggests that nifedipine appears to be a reasonable agent for treatment of acute severe hypertension in pregnancy. However, in a 1999 survey of Canadian practitioners, most stated that they rarely or never use nifedipine capsules for treatment of acute severe pregnancy hypertension. Also, there are case reports of adverse outcomes following use of nifedipine capsules in pregnancy, although the risks appear to have been overplayed.We suggest that a reasonable approach is ongoing use of nifedipine capsules, with perhaps an initial dosage of 5 mg rather than 10 mg. Having women swallow the capsule without first biting it may also be a prudent approach, because there is insufficient information from most of the published clinical trials to say exactly how the nifedipine capsules were administered. Further, use of the 10 mg nifedipine prolonged action tablet may also be a reasonable approach for treatment of severe hypertension in pregnancy, although more data are needed. Such research would be particularly relevant given that nifedipine appears to be a promising treatment for spontaneous preterm labour.We must resist the temptation to throw out of our limited therapeutic armamentarium an effective oral preparation before adequately considering the evidence.