Quality by design (QbD) and process analytical technology (PAT) applications in pharmaceutical industry

Quality by Design (QbD) for the pharmaceutical industry includes the design, development and production control of products and production processes from the beginning to the end of the product development phase for ensuring the consistent quality of a pharmaceutical product. The QbD is a systematic scientific approach aimed at meeting the needs of the patient in the desired and targeted quality and aiming to produce the same quality pharmaceutical product in this direction. Process Analytical Technology, which is assessed in that regard, is part of a design quality approach that is used to design, analyze, and control real-time measurements of quality and performance criteria for raw and processed materials to achieve the desired final product. This scientific and systematic approach to pharmaceutical product development, which is also acknowledged and supported by the health authorities, serves to the changing and developing pharmaceutical sector

Evaluation of the effect of topical and systemic ozone application in periodontitis: an experimental study in rats

Objective: The goal of the present study was to determine the effect of systemic and topical ozone application on alveolar bone loss (ABL) by evaluating the effect of Hypoxia-inducible factor −1 alpha (HIF-1-α) and receptor activator of NF-kB ligand (RANKL)-positive cells on histopathological and immunohistochemical changes in a rat periodontitis model. Methodology: Thirty male Wistar rats were divided into three groups: 1) Group C (control group); 2) Group SO (systemic ozone group) and 3) Group TO (topical ozone group). Experimental periodontitis was induced with a 3/0 silk suture placed at the mandibular left first molars of rats, and the suture was removed 14 days later. Ozone gas was injected intraperitoneally (0.7 mg/kg) in SO group. Topical ozone application protocol was performed using an ozone generator at 80% concentration (4th grade) 90- degree probe for the duration of 30 s. Both ozone applications were carried out for two weeks at intervals of two days. Histomorphometric and immunohistochemical analysis were performed. Results:ABL was significantly lower in Group SO compared to Group C (p: 0.0052). HIF-1α- positive cells were significantly lower in Group TO than in Group C (p: 0.0043). RANKL-positive cells were significantly lower in Group SO and in Group TO compared to the control group (p: 0.0033, p: 0.0075, respectively). Conclusion: Both ozone applications decreased RANKL-positive cell counts, TO application decreased HIF-1-α positive cells counts, and SO application was found to be more effective in reducing ABL compared to control group

Low serum levels of meteorin-like/subfatin: an indicator of diabetes mellitus and insulin resistance?

Introduction: Meteorin-like (Metrnl), also known as subfatin, is a recently discovered adipokine with a favourable effect on insulin sensitivity. Studies have shown lower Metrnl levels in obese patients. However, data on its circulating levels in type 2 diabetes mellitus (T2DM) patients are contradictory. This study aims to evaluate serum Metrnl levels in T2DM patients and determine the relationship between serum Metrnl levels and insulin resistance in these patients. Material and methods: This cross-sectional study was conducted among 150 participants. The study was carried out between June 2019 and December 2019 at the internal medicine outpatient clinic of a tertiary university hospital. The participants were divided into three groups: group 1 (control group, n = 50), group 2 (newly diagnosed T2DM, n = 50), and group 3 (long-standing diagnosed T2DM, n = 50). An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Subfatin (Metrnl), and the correlations of Metrnl level with anthropometric parameters, HOMA index, and biochemical measurements were assessed. Results: There was no statistically significant difference between the gender (p = 0.468) and age (p = 0.067) characteristics of the three groups. The Metrnl (subfatin) levels of the participants were as follows: control group – 20.05 (1.56–103.78); newly diagnosed T2DM group – 2.62 (1.25–103.78); and long-standing diagnosed T2DM group – 2.01 (0.80–19.84) pg/mL. The Metrnl (subfatin) levels of the participants in the control group were higher than in the participants in the newly diagnosed T2DM and long-standing diagnosed T2DM groups (p < 0.001). Subfatin demonstrated a negative correlation with insulin and HOMA-IR in the control group and long-standing diagnosed T2DM group. Conclusions: The subfatin level was found to be higher in the healthy control group than in both diabetic patient groups. Subfatin level showed negative correlation with both insulin level and HOMA index. There was a relationship between subfatin and insulin resistance. Low levels of subfatin in the diabetic patient groups may play a role in the pathogenesis of T2DM by increasing insulin resistance

Extreme Calvarial and Upper Cervical Hyperpneumatization: A Case Report

The pneumatization of bones of cranial base other than the mastoid process and temporal bone is a pathologic and rare condition, and it may cause some serious complications. Extension of the pneumatization to the cranial vault and upper cervical bones is extremely rare. A 67 year-old man was admitted with complaint of chronic nonspecific headache for a long time. He had no history of head trauma or otologic infection. Physical examination not revealed fever, any palpable swelling, rhinorrhea or otorrhea. There was only a slight right sensorineural hearing loss. Brain computerized tomography (CT) revealed hyperpneumatization in the right mastoid process and right temporal bone, bilateral occipital, parietal and frontal bones, and right side of the atlas. There was no pneumocephalus, but there was free air under the scalp of the right suboccipital region and around the right condyle, right transverse process of the atlas and right paravertebral region of the upper cervical vertebrae. Extrathecal cerebrospinal fluid (CSF) leakage was not detected by CT cisternography with intrathecal contrast administration and by the radionuclide cisternogram

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension