Safety and feasibility of rotational atherectomy (RA) versus conventional stenting in patients with chronic total occlusion (CTO) lesions: a systematic review and meta-analysis.

BACKGROUND AND AIM: Interventional cardiologists face challenges in managing chronic total occlusion (CTO) lesions, with conflicting results when comparing rotational atherectomy (RA) to conventional PCI. This meta-analysis aims to provide a critical evaluation of the safety and feasibility of RA in CTO lesions. METHODS: PubMed, Scopus, Web of Science, Ovid, and Cochrane central library until April 2023 were searched for relevant studies. MACE was our primary outcomes, other outcomes were all cause of death, cardiac death, MI, and TVR. Also, we reported angiographic outcomes as technical success, procedural success, and procedural complications in a random effect model. The pooled data was analyzed using odds ratio (OR) with its 95% CI using STATA 17 MP. RESULTS: Seven studies comprising 5494 patients with a mean follow-up of 43.1 months were included in this meta-analysis. Our pooled analysis showed that RA was comparable to PCI to decrease the incidence of MACE (OR = 0.98, 95% CI [0.74 to 1.3], p = 0.9). Moreover, there was no significant difference between RA and conventional PCI in terms of other clinical or angiographic outcomes. CONCLUSION: Our study showed that RA had comparable clinical and angiographic outcomes as conventional PCI in CTO lesions, which offer interventional cardiologists an expanded perspective when addressing calcified lesions. PROSPERO REGISTRATION: CRD42023417362.

Comparative Study of Lepidium Sativum Orally Administered Seeds, Hydrogel and Atorvastatin on Obesity of Rats Fed on a High Fat Diet.

BACKGROUND: Obesity has become a prevalent issue worldwide, leading to various complications such as hyperlipidemia, diabetes, and cardiovascular problems. Statins as FDA approved anti-hyperlipidemic drugs, still poses some concerns upon their administration. Recently, researchers have looked for natural products as an alternative to manage hyperlipidemia and obesity. AIM: This work aimed to study the hypolipidemic effect of Lepidium Sativum Garden Cress (GC) from different preparations; orally administered seeds, and hydrogel, in comparison to atorvastatin. METHODS: GC hydrogel was prepared from the GC aqueous extract and pharmaceutically evaluated for its pH, spreadability, seeds content, homogeneity, rheology, and in vitro release. The rat's body weight, blood glucose levels, total lipid profile, and liver biomarkers were evaluated on obese rats for one month. In addition, the histopathology study was also performed. RESULTS: GC hydrogel had acceptable pharmaceutical properties and showed a sustained release performance over 24 h. Oral and topical GC significantly reduced the lipid profiles, blood sugar and ALT, AST levels more than the negative control group and comparable to atorvastatin. It was found that oral GC showed a significant effect on the percentage decrease in the rat's body weight than the applied hydrogel. Histopathology study revealed a better outcome in the histological structure of pancreas and liver compared with rats feed on high fat diet post treatment for one month. CONCLUSION: GC orally administered, or topically applied hydrogel could be a promising, safe alternative formulation to atorvastatin in managing hyperlipidemia and normalizing body weight of obese rats.

The beneficial use of nitric oxide during cardiopulmonary bypass on postoperative outcomes in children and adult patients: a systematic review and meta-analysis of 2897 patients.

PURPOSE: Investigate inhaled nitric oxide's influence on mortality rates, mechanical ventilation and cardiopulmonary bypass duration, and length of stay in the intensive care unit and hospital when administered during cardiopulmonary bypass. METHODS: Following the PRISMA guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) up to 4th March 2023. The protocol was registered in the PROSPERO database with ID: CRD42023423007. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). RESULTS: The meta-analysis included a total of 17 studies with 2897 patients. Overall, there were no significant differences in using nitric oxide over control concerning mortality (RR = 1.03, 95% CI 0.73 to 1.45; P = 0.88) or cardiopulmonary bypass duration (MD = -0.14, 95% CI - 0.96 to 0.69; P = 0.74). The intensive care unit days were significantly lower in the nitric oxide group than control (MD = -0.80, 95% CI - 1.31 to -0.29; P = 0.002). Difference results were obtained in terms of the length of stay in the hospital according to sensitivity analysis (without sensitivity [MD = -0.41, 95% CI - 0.79 to -0.02; P = 0.04] vs. with sensitivity [MD = -0.31, 95% CI - 0.69 to 0.07; P = 0.11]. Subgroup analysis shows that, in children, nitric oxide was favored over control in significantly reducing the duration of mechanical ventilation (MD = -4.58, 95% CI - 5.63 to -3.53; P < 0.001). CONCLUSION: Using inhaled nitric oxide during cardiopulmonary bypass reduces the length of stay in the intensive care unit, and for children, it reduces the duration of mechanical ventilation.

Mixing of low-dose cohesive drug and overcoming of pre-blending step using a new gentle-wing high-shear mixer granulator.

The objective of this study was to examine the influence of drug amount and mixing time on the homogeneity and content uniformity of a low-dose drug formulation during the dry mixing step using a new gentle-wing high-shear mixer. Moreover, the study investigated the influence of drug incorporation mode on the content uniformity of tablets manufactured by different methods. Albuterol sulfate was selected as a model drug and was blended with the other excipients at two different levels, 1% w/w and 5% w/w at impeller speed of 300 rpm and chopper speed of 3000 rpm for 30 min. Utilizing a 1 ml unit side-sampling thief probe, triplicate samples were taken from nine different positions in the mixer bowl at selected time points. Two methods were used for manufacturing of tablets, direct compression and wet granulation. The produced tablets were sampled at the beginning, middle, and end of the compression cycle. An analysis of variance analysis indicated the significant effect (p < .05) of drug amount on the content uniformity of the powder blend and the corresponding tablets. For 1% w/w and 5% w/w formulations, incorporation of the drug in the granulating fluid provided tablets with excellent content uniformity and very low relative standard deviation (∼0.61%) during the whole tableting cycle compared to direct compression and granulation method with dry incorporation mode of the drug. Overall, gentle-wing mixer is a good candidate for mixing of low-dose cohesive drug and provides tablets with acceptable content uniformity with no need for pre-blending step.

New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X1), impeller speed (X2), wet massing time (X3), and water addition rate (X4) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p < .05) effect on granules and tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

NEW METHODOLOGY FOR DEVELOPMENT OF ORODISPERSIBLE TABLETS USING HIGH-SHEAR GRANULATION PROCESS.

Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granulation process as a new methodology for development of orodispersible tablets of high quality attributes using design of experiment approach. A two factor, three levels (32), full factorial design was carried out to investigate the main and interaction effects of independent variables, water amount (XI) and granulation time (X2) on the characteristics of granules and final product, tablet. The produced granules were analyzed for their granule size, density and flowability. Furthermore, the produced tablets were tested for: weight variation, breaking force/ crushing strength, friability, disintegration time and drug dissolution. Regression analysis results of multiple linear models showed a high correlation between the adjusted R-squared and predicted R-squared for all granules and tablets characteristics, the difference is less than 0.2. All dependent responses of granules and tablets were found to be impacted significantly (p < 0.05) by the two independent variables. However, water amount demonstrated the most dominant effect for all granules and tablet characteristics as shown by higher its coefficient estimate for all selected responses. Numerical optimization using desirability function was performed to optimize the variables under study to provide orodispersible system within the USP limit with respect of mechanical properties and disintegration time. It was found that the higher desirability (0.915) could be attained at the low level pf water (180 g) and short granulation time (1.65 min). Eventually, this study provides the formulator with helpful information in selecting the proper level of water and granulation time to provide an orodispersible system of high crushing strength and very low disintegration time, when high shear granulation methodology was used as a method of manufacture.

HIGH SHEAR GRANULATION PROCESS: ASSESSING IMPACT OF FORMULATION VARIABLES ON GRANULES AND TABLETS CHARACTERISTICS OF HIGH DRUG LOADING FORMULATION USING DESIGN OF EXPERIMENT METHODOLOGY.

High shear wet granulation is a significant component procedure in the pharmaceutical industry. The objective of the study was to investigate the influence of two independent formulation variables; polyvinypyrrolidone (PVP) as a binder (X,) and croscarmellose sodium (CCS) as a disintegrant (X2) on the crit- ical quality attributes of acetaminophen granules and their corresponding tablets using design of experiment (DoE) approach. A two factor, three level (32) full factorial design has been applied; each variable was investi- gated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their density, granule size and flowability. Additionally, the produced tablets have been investigated for: break- ing force, friability, disintegration time and t. of drug dissolution. The analysis of variance (ANOVA) showed that the two variables had a significant impact (p < 0.05) on granules and tablets characteristics, while only the binder concentration influenced the tablets friability. Furthermore, significant interactions (p < 0.05) between the two variables, for granules and tablets attributes, were also found. However, variables interaction showed minimal effect for granules flowability as well as tablets friability. Desirability function was carried out to opti- mize the variables under study to obtain product within the USP limit. It was found that the higher desirability (0.985) could be obtained at the medium level of PVP and low level of CCS. Ultimately, this study supplies the formulator with beneficial tools in selecting the proper level of binder and disintegrant to attain product with desired characteristics.

HIGH-SHEAR GRANULATION PROCESS: INFLUENCE OF PROCESSING PARAMETERS ON CRITICAL QUALITY ATTRIBUTES OF ACETAMINOPHEN GRANULES AND TABLETS USING DESIGN OF EXPERIMENT APPROACH.

Application of quality by design (QbD) in high shear granulation process is critical and need to recognize the correlation between the granulation process parameters and the properties of intermediate (granules) and corresponding final product (tablets). The present work examined the influence of water amount (X,) and wet massing time (X2) as independent process variables on the critical quality attributes of granules and corresponding tablets using design of experiment (DoE) technique. A two factor, three level (32) full factorial design was performed; each of these variables was investigated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their size distribution, density and flow pattern. Additionally, the produced tablets have been investigated for weight uniformity, crushing strength, friability and percent capping, disintegration time and drug dissolution. Statistically significant impact (p < 0.05) of water amount was identified for granule growth, percent fines and distribution width and flow behavior. Granule density and compressibility were found to be significantly influenced (p < 0.05) by the two operating conditions. Also, water amount has significant effect (p < 0.05) on tablet weight unifornity, friability and percent capping. Moreover, tablet disintegration time and drug dissolution appears to be significantly influenced (p < 0.05) by the two process variables. On the other hand, the relationship of process parameters with critical quality attributes of granule and final product tablet was identified and correlated. Ultimately, a judicious selection of process parameters in high shear granulation process will allow providing product of desirable quality.

Massive Hemoptysis: An Unusual Complication of Left Atrial Appendage Occlusion Device in Two Patients.

Left atrial appendage occlusion (LAAO) devices have emerged as a promising alternative for stroke prevention in non-valvular atrial fibrillation (NVAF) patients with contraindications to chronic anticoagulation therapy. The most common life-threatening procedural complications described in the literature include pericardial effusion, air embolism, and stroke. We here present a case report of two patients who experienced identical but rare post-procedural complications of pulmonary venous bleed, presenting as hemoptysis.

Effectiveness of Erector Spinae Plane Block as Perioperative Analgesia in Midline Sternotomies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: With the advancements in regional anesthesia and ultrasound techniques, the use of non-neuraxial blocks like the erector spinae plane block (ESPB) has been increasing in cardiac surgeries with promising outcomes. A total of 3,264 articles were identified through a literature search. Intervention was defined as ESPB. Comparators were no regional technique performed or sham blocks. Four studies with a total of 226 patients were included. Postoperative opioid consumption was lower in the group that received ESPB than the group that did not (weighted mean difference [WMD]: -204.08; 95% CI: -239.98 to -168.19; P < 0.00001). Intraoperative opioid consumption did not differ between the two groups (WMD: -398.14; 95% CI: -812.17 to 15.98; P = 0.06). Pain scores at 0 hours were lower in the group that received ESPB than the group that did not (WMD: -1.27; 95% CI: -1.99 to -0.56; P = 0.0005). Pain scores did not differ between the two groups at 4-6 hours (WMD: -0.79; 95% CI: -1.70 to 0.13; P = 0.09) and 12 hours (WMD: -0.83; 95% CI: -1.82 to 0.16; P = 0.10). Duration of mechanical ventilation in minutes was lower in the group that received ESPB than the group that did not (WMD: -45.12; 95% CI: -68.82 to -21.43; P = 0.0002). Given the limited number of studies and the substantial heterogeneity of measured outcomes and interventions, further studies are required to assess the benefit of ESPB in midline sternotomies.

Accuracy of procalcitonin for diagnosing sepsis in adult patients admitted to the emergency department: a systematic review and meta-analysis.

BACKGROUND: Differentiating sepsis from non-infectious systemic inflammatory response syndrome (SIRS) is challenging. Biomarkers like procalcitonin (PCT) aid early risk assessment and guide antibiotic use. This study aims to ascertain PCT's accuracy as a sepsis biomarker among adult emergency department admissions. METHOD: The PRISMA guidelines were followed to search for relevant articles in five electronic databases between April 14th and August 4th, 2023: PubMed, Cochrane Library, ProQuest, EMBASEs, and ScienceDirect. Studies had to be published in English to avoid directly translating scientific terms. Besides, the inclusion criteria were based on the diagnosis of sepsis in adult patients admitted to an emergency department. QUADAS-2 tool provided by the Review Manager version 5.4.1 was utilized to assess the risk of bias in included studies. STATA (v. 16) software was used to perform the meta-analysis. RESULTS: Ten of 2457 studies were included. We sampled 2980 adult sepsis patients for the under-investigated role of PCT in ED sepsis diagnosis. PCT emerged as the primary early diagnostic biomarker with high levels (29.3 ± 85.3 ng/mL) in sepsis patients. Heterogeneity in outcomes, possibly due to bias in cohort and observational studies, was observed. CONCLUSION: PCT tests offer moderate accuracy in diagnosing sepsis and stand out for rapidly and precisely distinguishing between viral and bacterial inflammations.

Comparative Analysis of Intravenous Opioids Versus Thoracic Epidural Anesthesia in Fractured Rib Pain Management: A Systematic Review and Meta-Analysis.

Rib fractures, common among trauma victims, lead to significant morbidity and mortality. Managing the associated pain is challenging, with IV opioids and thoracic epidural analgesia (TEA) being utilized. While epidural analgesia is often preferred for fractured rib pain, existing data encompasses both lumbar and thoracic approaches. This review aimed to compare TEA and IV opioids for persistent rib fracture pain. A comprehensive search across five databases yielded 987 articles, of which seven met the eligibility criteria. Outcomes were categorized into primary (pain reduction) and secondary (mortality, hospital/ICU stays, analgesia-related complications) endpoints. Analyzed with Review Manager (RevMan) Version 5.4.1 (2020; The Cochrane Collaboration, London, United Kingdom), the pooled data from two sources showed TEA significantly more effective in reducing pain than IV opioids (standardized mean difference (SMD): 2.23; 95%CI: 1.65-2.82; p < 0.00001). Similarly, TEA was associated with shorter ICU stays (SMD: 0.73; 95%CI: 0.33-1.13; p = 0.0004), while hospitalization duration showed no substantial difference (SMD: 0.82; 95%CI: -0.34-1.98). Mortality rates also did not significantly differ between TEA and IV opioids (risk ratio (RR): 1.20; 95%CI: 0.36-4.01; p = 0.77). Subgroup analysis revealed fewer pneumonia cases with TEA (RR: 2.06; 95%CI: 1.07-3.96; P = 0.03), with no notable disparities in other complications. While TEA's superiority in pain relief for rib fractures suggests it is the preferred analgesic, the recommendation's strength is tempered by the low methodological quality of supporting articles.

The Effect of Sedation on Diagnostic Lumbar Medial Branch Blocks for Facetogenic Low Back Pain: An Observational Study.

BACKGROUND: Lumbar medial branch blocks (MBB) are some of the most commonly performed pain procedures in the United States. Diagnostic MBBs are performed to confirm if the generator of low back pain is the facet joint. However, with diagnostic injections, false positive blocks may occur. OBJECTIVES:   Our prospective observational study aims to investigate the effects of midazolam sedation on patients' perceived intensity of pain relief following lumbar MBB. STUDY DESIGN: This is a single-center multi-site prospective observational study registered on clinicaltrials.gov (NCT04453449). SETTING: The study was approved by the Henry Ford Health System Institutional Review Board (IRB) in June 2020 (IRB# 14010) and registered on clinicaltrials.gov in July 2020 (NCT04453449). This manuscript adheres to the applicable EQUATOR STROBE guidelines for an observational cohort study. METHODS: Patients that underwent MBB without sedation were compared to sedated patients. Patients were asked to complete the Numeric Rating Scale (NRS) at baseline, one day after their diagnostic blocks, as well as 4 weeks and 8 weeks after their lumbar radiofrequency ablation (RFA). The primary outcome is the difference between baseline NRS pain scores and the lowest reported score in the 8 hours following MBB. For patients who proceed to RFA, the frequency of false positive blocks was evaluated. A patient was considered to have a false positive block when they failed to achieve 50% pain relief from RFA after 2 successful sequential MBBs. RESULTS: There was no significant difference in the NRS pain score change between the sedated and non-sedated groups for diagnostic block one (P = 0.167) and diagnostic block 2 (P = 0.6145). There was no significant difference of false positive rates between non-sedation and sedation patients at 4-weeks post-RFA (P = 0.7178) and at 8-weeks post-RFA (P = 1.000). LIMITATIONS: Some of the limitations of this study include its nonrandomized design, patient self-reported pain scores, as well as the small variability in the injection technique of proceduralists and in the anatomical location of the injection site. CONCLUSIONS: This study showed that midazolam did not change patients' perceived intensity of pain following MBB, as well as false positive rates after RFA. Larger studies are required to draw definitive conclusions.

Influence of Carbopol 71G-NF on the release of dextromethorphan hydrobromide from extended-release matrix tablets.

The objective of this study was to evaluate the potential of Carbopol(®) 71G-NF on the release of dextromethorphan hydrobromide (DM) from matrix tablets in comparison with hydroxypropyl methylcellulose (HPMC(®) K15M) and Eudragit(®) L100-55 polymers. Controlled release DM matrix tablets were prepared using Carbopol 71G-NF, HPMC K15M, and Eudragit L100-55 at different drug to polymer ratios by direct compression technique. The mechanical properties of the tablets as tested by crushing strength and friability tests were improved as the concentration of Carbopol, HPMC, and Eudragit increased. However, Carbopol-based tablets showed a significantly (P<0.05) higher crushing strength and a lower friability than HPMC and Eudragit tablets. No significant differences in weight uniformity and thickness values were observed between the different formulations. It was also found that Carbopol significantly (P<0.05) delayed the release of DM in comparison with HPMC K15M and Eudragit L100-55. A combination of HPMC K15M and Eudragit L100-55 in a 1:1 ratio at 20 and 30% significantly (P<0.05) delayed the release of DM than Eudragit L100-55 alone. Moreover, blends of Carbopol and HPMC at a 1:1 ratio at the 10, 20, and 30% total polymer concentration were investigated. The blend of Carbopol and HPMC at 10% level significantly (P<0.05) slowed the release of DM than Carbopol or HPMC alone, whereas blends at 20 and 30% level significantly (P<0.05) delayed the release of DM compared with HPMC or Carbopol alone. The results with these polymer blends showed that it was possible to reduce the total amount of polymers when used as a combination in formulation.

Full-Term Delivery and Complete Lung Recovery following VV ECMO Support Midpregnancy in a Patient with COVID-19 ARDS.

Pregnant women are especially vulnerable to coronavirus disease 2019 (COVID-19). We present a twin pregnancy case with acute respiratory distress syndrome following COVID-19 infection at 19 weeks. The patient's ARDS was successfully managed with veno-venous extracorporeal membrane oxygenation (VV ECMO). She recovered completely and delivered healthy twins.

Apneic Oxygenation: A Summarized Review and Stepwise Approach.

Apneic oxygenation is a technique used during airway management procedures to maintain oxygenation and prevent desaturation during a lack of ventilation. Despite its importance, there is a lack of comprehensive information on how to achieve effective apneic oxygenation, leading to misunderstandings and suboptimal utilization of this technique. Apneic oxygenation involves several key steps. Firstly, patient selection is crucial, considering factors such as anticipated difficulty with airway management, reduced functional residual capacity, increased oxygen consumption, and medical conditions associated with impaired oxygenation. Secondly, adequate preoxygenation is essential to optimize oxygen reserves before the onset of apnea, utilizing methods like non-rebreather oxygen masks or specific breathing techniques. Thirdly, maintaining airway patency through techniques such as jaw thrust or nasopharyngeal airway placement allows for unobstructed airflow during the apneic period. Lastly, the selection of the appropriate oxygen delivery method, such as high-flow nasal oxygen or nasal cannula, depends on the patient's existing respiratory support. Despite the growing body of literature on apneic oxygenation, current review articles often lack a stepwise approach for its proper execution. This knowledge gap contributes to the misunderstanding and underutilization of this important tool during intubation and airway management. In conclusion, apneic oxygenation is a valuable technique for maintaining oxygenation during periods of apnea. However, the lack of comprehensive information and stepwise guidance in the current literature hinders its optimal utilization. Clear guidelines and educational resources should be developed to address this knowledge gap and ensure the safe and effective implementation of apneic oxygenation. By following a stepwise approach that includes patient selection, adequate preoxygenation, airway patency, and appropriate oxygen delivery, healthcare providers can enhance patient outcomes and minimize the risk of desaturation during airway management procedures.

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology.

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica.

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 32 full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X1) and mixing time (X2). Flow, bulk density, and compaction properties of CNG-silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X1 and X2 on the characteristics of CNG with a predominant effect of X1. Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process.

ß1-adrenergic receptor polymorphisms: a possible genetic predictor of bisoprolol response in acute coronary syndrome.

Aim: To investigate the association between beta1-adrenergic receptor (ADRB1) polymorphisms and response to bisoprolol treatment in beta-blocker naive patients with acute coronary syndrome (ACS). Patients & methods: Seventy-seven patients received bisoprolol for four weeks. Blood pressure and heart rate were measured at baseline and during treatment. TaqMan allelic discrimination method was utilized for ADRB1 Ser49Gly and Arg389Gly genotyping. Results: Arg389Arg carriers showed greater reductions in systolic and diastolic blood pressure (-8.5% ± 7.8% vs -0.76% ± 8.7%, p = 0.000218), and (-9.5% ± 9.7% vs -0.80% ± 11.5%, p = 0.000149), respectively, compared with Gly389 carriers. No statistical difference was found for study's outcomes based on codon 49. Conclusion: Arg389Gly polymorphism is a promising bisoprolol response predictor in ACS patients.

Pharmacogenetics is a field of study that explores how our genes can affect how well certain medicines work. In this study, scientists looked at a specific gene called beta1-adrenergic receptor to see how it can influence a drug called bisoprolol. They wanted to find out if some people's genes made bisoprolol work better for them. They studied 77 patients with a heart problem called acute coronary syndrome (ACS) who were taking bisoprolol for 4 weeks. The researchers discovered that people with a particular gene piece called Arg389Arg responded better to bisoprolol. They had bigger reductions in their blood pressure compared with those who had a different gene called Gly389. This finding suggests that by looking at a person's genes, doctors might be able to predict how well bisoprolol will work for them. This way, doctors can choose the best treatment for each patient, making sure they get the most benefit from the medicine.