Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of solubility and dissolution rate

Nimodipine (NMD) is a dihydropyridine calcium channel blocker useful for the prevention and treatment of delayed ischemic effects. It belongs to class ? drugs, which is characterized by low solubility and high permeability. This research aimed to prepare Nimodipine nanoparticles (NMD NPs) for the enhancement of solubility and dissolution rate. The formulation of nanoparticles was done by the solvent anti-solvent technique using either magnetic stirrer or bath sonicator for maintaining the motion of the antisolvent phase. Five different stabilizers were used to prepare NMD NPs( TPGS, Soluplus®, HPMC E5, PVP K90, and poloxamer 407). The selected formula F2, in which Soluplus has been utilized as a stabilizer, has a particle size (77 nm) and polydispersity index (PDI) (0.016). The formulas with the smallest particle size were freeze dried with the addition of 1 % w/w mannitol as cryoprotectant. The saturation solubility of NMD in the prepared nanoparticles was increased twenty four-folds, and the complete dissolution was achieved at 90 minutes compared with pure NMD, which reaches only 6%. The formation of hydrogen bonding between NMD and the polymer or the cryoprotectant, as confirmed by the FTIR study. In conclusion, the preparation of NMD as polymeric nanoparticles is a useful technique for enhancing the solubility and dissolution rate.

Effect of Dihydropyridine Calcium-Channel Blocker on Adverse Aortic Events After Thoracic Endovascular Aortic Repair for Type B Aortic Dissection

Objectives: This study aimed to evaluate the effect of dihydropyridine calcium-channel blocker (CCB) on adverse aortic events (AAE) in patients undergoing thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). Methods: A retrospective study was conducted on patients undergoing TEVAR of TBAD from January 2010 to December 2017 in our center. Patients were divided into CCB group and non-CCB group according to the postoperative dihydropyridine CCB use. AAE including aorta-relative mortality and reintervention, were compared between these two groups. Propensity score matching analysis was performed to avoid the potential effect of known confounders.Results: Before matching, the study cohort comprised 548 patients, including 435 (79.4%) and 113 (20.6%) patients in the CCB and non-CCB groups, respectively. After matching, 101 patients in each group were eligible for the analysis. In the unmatched cohort, AAE occurred in 52 (12.0%) and 29 (25.7%) patients in the CCB and non-CCB groups, respectively (P < 0.001). In the matched cohort, AAE occurred in 8 (7.9%) and 22 (21.8%) patients in the CCB and non-CCB groups, respectively (P = 0.013). Log-rank test analysis revealed that the levels of freedom from AAE were significantly different between the 2 groups in both the unmatched and matched cohorts (P < 0.001 and P = 0.007, respectively). Multivariable analysis showed that CCB use (hazard ratio 0.50, 95% confidence interval 0.32–0.80; P = 0.003) was associated with a lower AAE rate after adjustment for other variables, and was minimally changed after the propensity score matching (HR 0.34, 95% CI 0.15–0.75; P = 0.008).Conclusions: Postoperative dihydropyridine CCB use is protective in patients undergoing TEVAR for acute and sub-acute TBAD.

Formulation Development of Nifedipine through Nanotechnology: A Comprehensive Review

Background: The therapeutic use of nifedipine, a dihydropyridine calcium channel blocker, is limited due to its poor solubility profile, rapid onset of its action, and short biological half-life. Many formulation techniques have been applied to improve the properties of the drug. Objective: The objective of the study is to summarize the nanotechnology approaches designed to improve the therapeutic and pharmacokinetic properties of nifedipine till 2020. Methods: The related articles were searched until 28th March, 2020, with the specific keywords, in Pubmed and google scholar, excluding review articles. Results: The discussion showed that among the nano-carriers used to improve the pharmacological property of the drug, lipid nanoparticles, polymeric nanoparticles, crystalline nanoparticles, and nano-emulsions have been used widely. Nanotechnology has been found efficient in improving the solubility profile of nifedipine, achieving sustained and controlled release, and achieving targeted and local delivery and transdermal drug delivery. By exploiting nano-formulations, new windows of therapeutic applications can be achieved. Furthermore, micelle media, polymeric nanoparticles, and microcrystalline nanoparticles have been used to develop a photostable formulation. Conclusion: The technological innovations in the field of nanomedicine have paved many ways for delivering nifedipine and such sparingly water-soluble compounds.

Optimizing Cardiovascular Outcome in Type 2 Diabetes Mellitus with Better Control of Diabetes Mellitus with Empigliflozin and Hypertension with Renin Angiotensin System Inhibitors and Manidipine Preferably of the Dihydropyridones

Aim Obesity is increasing globally by leaps and bounds and thus the incidence of type 2 diabetes mellitus (T2DM) along with it so much so that the term diabesity had to be coined. Earlier we had reviewed how to treat the both together and the role of empagliflozin to improve cardiovascular outcome trials (CVOT). Similarly T2DM and hypertension are pathophysiologically-related diseases which co-exist with a broader complex of metabolic diseases which co-exist possessing similar set of risk factors. Hence it is important to consider which antihypertensives are suitable that possess a positive effect on metabolic factors in cases of T2DM who require an antihypertensive. Method A systematic review was carried out using the PubMed search engine with the MeSH terms: “T2DM”; “essential hypertension; “cardiovascular (CV)”; “Complications of diabetes mellitus (DM) and antihypertensive”; “Antihypertensive preferred in T2DM subjects”; “Renin-angiotensin–aldosterone system inhibitors”; “Angiotensin converting enzyme inhibitors (ACEi)”; “Angiotensin receptor blockers (ARBs)”; “Dihydropyridine calcium channel blocker”; “β2 blockers”; “Diuretics”. Discussion Most diabetes mellitus (DM) subjects need a minimum of two antihypertensive drugs, combining a renin-angiotensinaldosterone system (RAS) inhibitor with a dihydropyridine calcium channel blocker seems to be the most indicated approach. But not all dihydropyridine calcium channel blockers have equivalent effects on metabolic parameters. Hence manidipine that causes positive effect on insulin resistance (IR) seems to be an effective option. We have reviewed how manidipine is superior to amlodipine with regards to improving IR, not seen with amlodipine, along with not causing excessive sympathetic nervous system (SNS) activation, pulse pressure and ankle edema or to much lesser extent than amlodipine. Therefore, manidipine needs to be the first addition to RAS inhibitors in case of DM’s having hypertension of the dihydropyridines calcium channel blockers. Further good blood pressure (BP) control been correlated with good CVs outcomes. Conclusion A RAS inhibitor is the first line of choice of drugs in a subject with T2DM who needs to be treated with empagliflozin for better CVOT outcome, and when a 2nd drug has to be added it is manidipine that is preferred over amlodipine. Plant products are proving to be having a lot of beneficial effects in DM, obesity and hypertension. Thus need for developing agents from plants will prove to be more cost effective in these chronic diseases where compliance is difficult to achieve with the use of common antiDM drugs and antihypertensives with the cost factor along with their side effects.

Development and validation of a UPLC-DAD method for the simultaneous quantification of eight antihypertensive drugs in the pharmaceutical matrix

Background Hypertension is a critical health problem; it is a prevalent risk factor for cardiovascular disease. Many treatments to combat hypertension are available, while several patients are resistant to the standard therapeutic approaches. The association of two or more substances in a fixed-dose combination is effective and tolerated to substitute the standard therapeutic approach. Objective New UPLC-DAD method was developed and validated to assay a combination of eight antihypertensive drugs including a diuretic: hydrochlorothiazide, dihydropyridine calcium channel blocker: Amlodipine and angiotensin II type 1 receptor blockers (sartans): valsartan, candesartan, eprosartan, olmesartan, losartan, and irbesartan in the pharmaceutical matrix. Methods Chromatographic separation was performed on an Acquity® UPLC C18 1.7 µm 2.1 × 100 mm column, with a gradient of buffer solution and acetonitrile, in the proportion of (80:20 v/v). Results Good resolution was obtained, and an optimal analysis time of less than 5 min was achieved. The method was validated according to the International Conference on Harmonization (ICH) guidelines following the classical approach and accuracy profile, it is shown to be suitable for intended applications. The method was successfully used for quality control laboratories and the determination of these drugs combination in pharmaceutical dosage forms.

Fixed combination in patients with arterial hypertension: focus on antihypertensive and nephroprotective properties of fixed combination of lisinopril and amlodipine (clinical example)

Arterial hypertension (AH) remains one of the most significant medical and social problems in the world, its prevalence among the adult population is 30–45%. Along with this, the modern population is characterized by a high incidence of chronic kidney disease (CKD), including due to their secondary damage in the framework of hypertension. In turn, CKD is an important independent risk factor for the development and progression of cardiovascular diseases, including fatal ones. The use of existing approaches to nephroprotection in the treatment of patients with hypertension will significantly improve the prognosis both in patients with risk factors for developing renal dysfunction and in patients with pre-existing kidney disease. According to current recommendations for hypertension in such clinical situations, therapy should begin with fixed combinations of antihypertensive drugs. The combination of an angiotensin converting enzyme inhibitor (ACE) and a dihydropyridine calcium channel blocker (CCВ) demonstrated the greatest effectiveness according to evidence-based medicine in patients with high-risk hypertension, including from the standpoint of nephroprotection. In the presented clinical case, the successful use of a fixed combination of ACE and CCВ in a patient with hypertension and microalbuminuria is described.

The use of antihypertensive medications in cancer patients on chemo immunotherapy: Protection or not?

e19238 Background: Antihypertensive medications is a widely used in the cancer patients due to comorbid hypertension. The following analysis was devoted to find if any particular group can provide nephroprotective effect for patient that is receiving chemo immunotherapy. Methods: A retrospective cohort of the 95 patients, who received chemo immunotherapy in the infusion center of Mercy Fitzgerald Hospital in 2018-2020 were analyzed. We divided patient in 4 groups. Those who were receiving beta-blockers - group 1, angiotensin-converting enzyme/angiotensin receptor blockers – group 2, dihydropyridine calcium channel blocker – group 3, non-dihydropyridine calcium channel blocker – group 4. KDIGO criteria were used to identify patients with Acute Kidney Injury (AKI). Chi-square test was used to estimate if there is association between using specific group of anti-hypertensives medications and AKI. Results: 12 out of 95 patients in the study developed AKI. In group 1 5 had AKI and 23 not, p = .032. Group 2 included 3 patient who developed AKI and 22 who did not, p = 0.91. Group 3 group had 6 patients with AKI and 10 without, p = 0.001. Group 4 had 10 patients and none of them had AKI, p = 0.16. Conclusions: In our study we found that patient who were using the dihydropyridine calcium channel blocker (amlodipine) had a higher incidence of the AKI then patients, who were using other groups of the anti-hypertensive medications. Large prospective studies may be necessary to confirm that use of amlodipine in patients who undergo chemo immunotherapy is associated with higher incidence of the AKI and should be avoided in the treatment of this patients.