One Factor at a Time and factorial experimental design for formulation of l-carnitine microcapsules to improve its manufacturability.

l-carnitine is an essential dietary supplement of physiological importance. Handling and manufacture of l-carnitine is difficult due to its hygroscopic nature, resulting in impairing its flow properties, as well as solid dosage form stability. The study aimed at reducing l-carnitine hygroscopicity through its encapsulation within a hydrophobic, pH-insensitive polymer. A solid in oil in oil (s/o/o) emulsion solvent evaporation technique for microencapsulation was adopted to exclude the possibility of water uptake. The polymers used were two ethyl cellulose (EC) grades with different viscosities. The chosen solvent for the polymer was acetone, and liquid paraffin was the dispersion medium in which both the drug and polymer were insoluble. Sixteen formulations were developed, and evaluated to study the formulation parameters as anti-coalescent type, mixing speed, surfactant type and polymer ratio, and viscosity grade. A "One Factor at A Time" (OFAT) design of experiment, and a factorial design were utilized. Study results revealed that successful microencapsulation occurred by using Aerosil 200 (0.1 %) as anti-coalescent, a mixing speed of 1000 rpm, and Ethocel Std 20 at a 3:1 drug-to-polymer ratio. Microcapsule formulation containing l-carnitine base, successfully compressed into tablets, showed acceptable water content, disintegration time, hardness, and dissolution. Moreover, it showed acceptable stability upon storage at 40 °C at 75 % RH for six months compared to l-carnitine tablets prepared by wet granulation.

Twice-Weekly Versus Once-Weekly Membrane Sweeping in the Prevention of Post-Term Pregnancy: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Membrane sweeping is considered a simple and effective method for initiating spontaneous onset of labor. Despite the widely accepted membrane sweeping use to prevent post-term birth, the optimal frequency has not been estimated. We aimed to assess the effectiveness and safety of twice-weekly versus once-weekly membrane sweeping in post-term pregnancy prevention. Four different databases were searched for available clinical trials from inception to October 2022. We selected randomized controlled trials (RCTs) that compared twice-weekly membrane sweeping in intervention group versus once-weekly membrane sweeping in control group among pregnant women with singleton pregnancy at ≥ 39 gestational weeks. Our primary outcomes were the rate of spontaneous onset of labor and the requirement for formal methods of labor induction. Our secondary outcomes were sweeping to delivery interval in days, gestational age at delivery in weeks, Bishop score at admission, chorioamnionitis, and premature rupture of membranes. Three RCTs (596 patients) were included. Twice-weekly membrane sweeping was associated with significant increase in the rate of spontaneous onset of labor and significant decline in labor induction rate in comparison with once-weekly group. Duration from sweeping to delivery was significantly shorter among the twice-weekly group (p<0.001). Furthermore, gestational age at delivery was significantly earlier in the twice-weekly group. A significantly higher Bishop score at admission was observed in the twice-weekly group (p=0.02). There were no significant differences across both groups in chorioamnionitis and premature rupture of membranes. In conclusion, twice-weekly membrane sweeping is more effective in preventing post-maturity pregnancy than once-weekly sweeping without added adverse events.

A new promising approach to urodynamic stress urinary incontinence care can help menopausal women.

Introduction: The goal of this study is to evaluate the effectiveness of single-incision mini-sling in the surgical treatment of postmenopausal urodynamic stress urinary incontinence (SUI) compared to the standard trans-obturator mid-urethral sling. Material and methods: This prospective study was carried out in two tertiary centres; Al-Azhar University Maternity & Urology Hospitals. A total of 120 postmenopausal women with urodynamic SUI were randomized to undergo either single-incision mini-sling (n = 60) or standard trans-obturator mid-urethral sling procedure (n = 60) from May 2019 until Oct 2021. Main outcome measures: efficacy was evaluated utilizing objective cure rate (cough stress test) and subjective cure rate (Sandvik incontinence severity index and International Consultations on Incontinence Questionnaire - Short Form), intraoperative and postoperative complications, and postoperative pain (using a visual analogue scale). Results: The single-incision mini-sling (SIMS) and transobturator tape (TOT) groups had no statistically significant difference in subjective and objective cure rates (p > 0.05). Compared with the transvaginal tape O group, patients in the SIMS group had significantly less postoperative pain, shorter operative duration, and less intraoperative blood loss (all p-values < 0.05). No significant difference in perioperative complications was observed between both groups. Conclusions: Single-incision mini-sling was superior to TOT in postmenopausal as SIMS is of similar effectiveness, more safe and minimally invasive with earlier ambulance.

A paradigm of higher success rate of intracytoplasmic sperm injection - preovulatory human chorionic gonadotropin-day serum oestradiol.

Introduction: The aim of the study is to evaluate the correlation between the level of serum oestradiol (E2) on the day of human chorionic gonadotropin (hCG-day) administration and successful intracytoplasmic sperm injection (ICSI) outcome. Material and methods: This prospective study was performed during the period from January 2019 to September 2021, at Zagazig Obstetrics and Gynecology Department, and Al-Azhar Obstetrics and Gynecology Department, and private ART centers. One hundred and fifty women attending the infertility clinic for ICSI cycles. All women were divided into 5 groups according to the serum E2 level on the day of hCG administration: Group A - serum E2 < 1000 pg/ml; Group B - serum E2 1000 to < 2000 pg/ml; Group C - serum E2 2000 to < 3000 pg/ml;Group D - serum E2 3000 to < 4000 pg/ml; Group E - serum E2 ≥ 4000 pg/ml. Results: The highest fertilization rate (58.1%) was among women with E2 ≥ 4000 pg/ml, while the lowest (37%) was in women with E2 1000 to < 2000 pg/ml. Also, the highest pregnancy rate (21.5%) was among women with E2 > 4000 pg/ml, while the lowest (5.3%) was in women with E2 < 1000 pg/ml. In the current study the median serum E2 level on the day of hCG administration was highly significant in women who became pregnant when compared to women who did not. The best cut-off value of serum E2 at hCG administration was ≥ 3682.3 pg/ml. Conclusions: this study suggests that the optimal range of E2 level for achieving a successful pregnancy is > 4000 pg/ml.

A novel injection technique for ilioinguinal nerve block for post-operative pain relief in caesarean delivery - a randomized, double-blind, placebo-controlled trial.

AIM: To determine whether the novel method is successful in blocking both ilioinguinal nerves to lessen postoperative pain following caesarean surgery. MATERIALS AND METHODS: Between January 2022 and January 2023, 300 patients were enrolled in this study at the Obstetrics and Gynaecology Departments of the Faculty of Medicine at Al-Azhar University. About 150 of these patients received bupivacaine infiltration on both sides close to the anterior superior iliac spine, and 150 received a normal saline injection at the same locations. RESULTS: The study compared the two groups and discovered significant differences in the timing of analgesic requests, interval before the patient's first ambulation, length of hospital stay, postoperative pain score, and incidence of postoperative nausea and vomiting, with group A performing better. CONCLUSION: After a caesarean section, the local anaesthetic "bupivacaine" injection used to block the ilioinguinal nerves bilaterally is an efficient way to lessen postoperative discomfort and analgesic use.

Effect of Vaginal Washing before Intravaginal Prostaglandin Insertion on Induction of Labor: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Saline vaginal douching prior to intravaginal prostaglandin application might increase the vaginal pH, leading to improvement of prostaglandin bioavailability, by which the outcomes of labor induction can be greatly improved. Thus, we aimed to evaluate the effect of vaginal washing with normal saline before insertion of vaginal prostaglandin for labor induction. STUDY DESIGN: A systematic search was done in PubMed, Cochrane Library, Scopus, and ISI Web of Science from inception to March 2022. We selected randomized controlled trials (RCTs) that compared vaginal washing using normal saline versus no vaginal washing in the control group before intravaginal prostaglandin insertion during labor induction. We used RevMan software for our meta-analysis. Our main outcomes were the duration of intravaginal prostaglandin application, duration from intravaginal prostaglandin insertion to active phase of labor, duration from intravaginal prostaglandin insertion till total cervical dilatation, labor induction failure rate, incidence of cesarean section (CS), and rates of neonatal intensive care unit (NICU) admission and fetal infection postdelivery. RESULTS: Five RCTs were retrieved with a total number of 842 patients. Duration of prostaglandin application, duration from prostaglandin insertion to active phase of labor, and time interval from prostaglandin insertion to total cervical dilatation were significantly shorter among vaginal washing group (p < 0.05). Vaginal douching prior to prostaglandin insertion significantly decreased the incidence of failed labor induction (p < 0.001). After the removal of reported heterogeneity, vaginal washing was linked to a significant decline in CS incidence (p = 0.04). In addition, the rates of NICU admission and fetal infection were significantly lower in the vaginal washing group (p < 0.001). CONCLUSION: Vaginal washing with normal saline before intravaginal prostaglandin insertion is a useful and easily applicable method for labor induction with good outcomes. KEY POINTS: · Induction of labor is frequently used in the obstetrics field.. · We assessed vaginal washing impact before prostaglandin insertion for labor induction.. · Vaginal washing is an easily applicable method for labor induction with good outcomes..

Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up.

L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate) were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33 full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant) concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.

Tubularised incised-plate versus tubularisation of an intact and laterally augmented plate for hypospadias repair: A prospective randomised study.

OBJECTIVES: To compare the outcome of hypospadias repair using tubularised incised-plate (TIP) urethroplasty and tubularisation of an intact and laterally augmented urethral plate. PATIENTS AND METHODS: This prospective randomised study included 370 patients with primary distal hypospadias. All had urethral plate widths of 8-10 mm and a glans of ⩾15 mm. Exclusion criteria were previous repair, circumcision, a wide urethral plate of >10 mm or a narrow plate of <8 mm in diameter, a small glans of <15 mm in diameter, chordee of >30°, and hormonal stimulation. Patients were randomised into two groups: Group 1 (185 patients) underwent TIP urethroplasty and Group 2 (185 patients) underwent tubularisation of the intact plate with lateral augmentation of the urethral plate using penile skin. The follow-up period was 12-28 months. RESULTS: There were 172 evaluable patients in Group 1 and 177 in Group 2. The urethroplasty was successful in 83.2% and 94.4% in Groups 1 and 2, respectively. Complications occurred in 16.8% in Group 1 and 5.6% in Group 2 (P = 0.001). Meatal stenosis occurred in 7% and 3.4% in Groups 1 and 2, respectively (P = 0.130). There were statistically significant differences in the wound dehiscence, fistula, and re-operation rates of Group 1 versus Group 2, at 6% versus 0%, 9.8% versus 2.8%, and 13.4% versus 5.6%, respectively. The presence of mild chordee did not affect the complication rate (P = 0.242). The mean (SD) operative time was 56.7 (8.9) min in Group 1 and 93.7 (8.3) min in Group 2 (P < 0.001). CONCLUSION: The outcome of tubularised intact and laterally augmented plate is better than classical TIP urethroplasty of hypospadias. Further trials are mandatory to extend the indications of the technique.