Trend of pharmaceuticals 3D printing in the Middle East and North Africa (MENA) region: An overview, regulatory perspective and future outlook.

The traditional method of producing medicine using the "one-size fits all" model is becoming a major issue for pharmaceutical manufacturers due to its inability to produce customizable medicines for individuals' needs. Three-dimensional (3D) printing is a new disruptive technology that offers many benefits to the pharmaceutical industry by revolutionizing the way pharmaceuticals are developed and manufactured. 3D printing technology enables the on-demand production of personalized medicine with tailored dosage, shape and release characteristics. Despite the lack of clear regulatory guidance, there is substantial interest in adopting 3D printing technology in the large-scale manufacturing of medicine. This review aims to evaluate the research efforts of 3D printing technology in the Middle East and North Africa (MENA) region, with a particular emphasis on pharmaceutical research and development. Our analysis indicates an upsurge in the overall research activity of 3D printing technology but there is limited progress in pharmaceuticals research and development. While the MENA region still lags, there is evidence of the regional interest in expanding the 3D printing technology applications in different sectors including pharmaceuticals. 3D printing holds great promise for pharmaceutical development within the MENA region and its advancement will require a strong collaboration between academic researchers and industry partners in parallel with drafting detailed guidelines from regulatory authorities.

Development and Characterization of Different Dosage Forms of Nifedipine/Indomethacin Fixed-Dose Combinations.

Studies have shown that 40 individuals out of 100,000 are diagnosed with rheumatoid arthritis (RA) yearly, with a total of 1.3 million in the United States. Furthermore, the impact of RA in some cases can extend to cardiovascular diseases (CVD), as the studies showed that 84% of RA patients are at risk of developing hypertension. This study aims to design and develop different dosage forms (capsule-in-capsule and three-dimensional (3D) printed tablet) of nifedipine/indomethacin fixed-dose combination (FDC). The hot-melt extrusion (HME) was utilized alone and with fused deposition modeling (FDM) techniques The developed dosage forms were intended to provide delayed-extended and immediate release profiles for indomethacin and nifedipine, respectively. FDC dosage forms were successfully developed and characterized. Nifedipine formulations showed significant improvement in release profiles, having 94% of the drug release at 30 minutes compared with pure nifedipine, which had a percent release of 2%. Furthermore, the release of indomethacin was successfully delayed at a pH of 1.2 and extended at a pH of 6.8. Differential scanning calorimetry results showed endothermic crystalline peaks at 165 °C and 176 °C for indomethacin and nifedipine, respectively. Moreover, the thermal analysis of all formulations showed the absence of the endothermic peaks indicating complete solubilization of indomethacin and nifedipine in the polymeric carriers. All formulations had post-processing drug content in the range of 95% to 98%. Moreover, results from the stability study showed that all formulations were able to remain chemically and physically stable with no signs of recrystallization or degradation. The designed FDC dosage forms could improve the quality of life by enhancing patient compliance and preventing the need for polypharmacy.

Investigation of hot melt extrusion process parameters on solubility and tabletability of atorvastatin calcium in presence of Neusilin® US2.

Reports in the literature indicate that hot-melt extrusion (HME) processing techniques could alter the mechanical properties of the pharmaceutical physical blend, which may alter successful processing during tableting. The aim of this study was to evaluate whether HME processing conditions have an impact on the tabletability of Atorvastatin calcium trihydrate (ATR) in the presence of Neusilin® US2 (NUS2). ATR drug load of 25% was mixed with 75% of NUS2 and extruded using two screw configurations, screw speeds, and feed rates. Solid-state thermal analysis showed that ATR transformed to an amorphous form which led to improved solubility. ATR tabletability was affected positively by screw configuration that had no shearing and mixing force. SEM analysis indicated that a conveying screw configuration preserved the spherical nature of NUS2, thus improving ATR tabletability. This novel study demonstrates the significance of changing and monitoring the HME process parameters, which impact the materials' mechanical properties and may prevent adverse outcomes during tableting.

Effect of pH Modifiers on the Solubility, Dissolution Rate, and Stability of Telmisartan Solid Dispersions Produced by Hot-melt Extrusion Technology.

The aim of the current study was to investigate the dual effect of an amorphous solid dispersion generated by hot melt extrusion and the addition of pH modifiers on the solubility and stability of telmisartan. Hydroxypropyl methylcellulose acetate succinate L grade was used as a polymeric carrier and recrystallization inhibitor, and meglumine, sodium carbonate, or Neusilin S2 were incorporated as pH modifiers to generate a desirable microenvironmental pH in the solid dispersions. Differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy were incorporated to obtain the solid-state characterizations of telmisartan, and the results confirm a partial transformation of telmisartan to an amorphous state. An in vitro release study revealed that the transformation of telmisartan to an amorphous material improved its dissolution rate by 2-fold compared to pure drug and by up to 5-fold with the incorporation of pH modifiers. Results of the stability studies demonstrated that the samples have no significant degradation under accelerated stability conditions at 40 °C/75% RH.

Formulation and evaluation of inhaled Sildenafil-loaded PLGA microparticles for treatment of pulmonary arterial hypertension (PAH): A novel high drug loaded formulation and scalable process via hot melt extrusion technology (Part â ).

In recent years, several techniques were employed to develop a local sustained pulmonary delivery of sildenafil citrate (SC) as an alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). Most of these methods, however, need to be improved due to limitations of scalability, low yield production, low drug loading, and stability issues. In this study, we report the use of hot-melt extrusion (HME) as a scalable process for making Poly (lactic-co-glycolic acid) (PLGA) microparticles with high SC load. The prepared particles were tested in vitro for local drug delivery to the lungs by inhalation. Sodium bicarbonate was included as a porogen in the formulation to make the particles more brittle and to impart favorable aerodynamic properties. Six formulations were prepared with different formulation compositions. Laser diffraction analysis was used to estimate the geometric particle size distribution of the microparticles. In-vitro aerodynamic performance was evaluated by the next-generation cascade impactor (NGI). It was reported in terms of an emitted dose (ED), an emitted fraction (EF%), a respirable fraction (RF%), a fine particle fraction (FPF%), a mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). The formulations have also been characterized for surface morphology, entrapment efficiency, drug load, and in-vitro drug release. The results demonstrated that PLGA microparticles have a mean geometric particle size between 6 and 14 µm, entrapment efficiency of 77 to 89 %, and SC load between 17 and 33 % w/w. Fifteen percent of entrapped sildenafil was released over 24 h from the PLGA microparticles, and seventy percent over 7 days. The aerodynamic properties included fine particle fraction ranging between 19 and 33 % and an average mass median aerodynamic diameter of 6-13 µm.

Exploring the Impact of Iron Deficiency Anaemia on Glycated Haemoglobin A1c Levels in Pregnant and Non-Pregnant Women: A Systematic Review.

Haemoglobin A1C (HbA1c) is fundamental in monitoring glycaemic control during pregnancy. However, several conditions could affect this test's accuracy, including iron deficiency anaemia (IDA). Hence, this systematic review delves into the underexplored connection between IDA, iron replacement therapy (IRT), and haemoglobin A1C (HbA1c) during pregnancy. An electronic search of the Cochrane, MEDLINE, and Embase databases was conducted by six authors. From a comprehensive search strategy, 968 records were obtained. After applying the inclusion and exclusion criteria, seven studies were included, comprising 365 women selected for analysis. Six studies indicated a positive correlation between IDA and HbA1c levels, while one found no correlation. The average HbA1c level of the included studies in pregnant women was 5.64%. In comparison, it was found that non-pregnant women had lower HbA1c levels. Among the included studies, the mean HbA1c levels decreased from 5.1% to 4.89% after treating pregnant women with IRT. The review emphasises the complexity of interpreting HbA1c levels in pregnant women with IDA, highlighting the influence of pregnancy-induced physiological changes. In addition, this suggests that HbA1c should not be the sole criterion for diabetes management in pregnant women with IDA. Future research should focus on alternative glycaemic monitoring methods unaffected by IDA.

Disulfiram 3D printed film produced via hot-melt extrusion techniques as a potential anticervical cancer candidate.

Cervical cancer is known globally as one of the most common health problems in women. Indeed, one of the most convenient approaches for its treatment is an appropriate bioadhesive vaginal film. This approach provides a local treatment modality, which inevitably decreases dosing frequency and improves patient compliance. Recently, disulfiram (DSF) has been investigated and demonstrated to possess anticervical cancer activity; therefore, it is employed in this work. The current study aimed to produce a novel, personalized three-dimensional (3D) printed DSF extended-release film using the hot-melt extrusion (HME) and 3D printing technologies. The optimization of the formulation composition and the HME and 3D printing processing temperatures was an important factor for overcoming the DSF heat-sensitivity issue. In addition, the 3D printing speed was specifically the most crucial parameter for alleviating heat-sensitivity concerns, which led to the production of films (F1 and F2) with an acceptable DSF content and good mechanical properties. The bioadhesion film study using sheep cervical tissue indicated a reasonable adhesive peak force (N) of 0.24 ± 0.08 for F1 and 0.40 ± 0.09 for F2, while the work of adhesion (N.mm) for F1 and F2 was 0.28 ± 0.14 and 0.54 ± 0.14, respectively. Moreover, the cumulative in vitro release data indicated that the printed films released DSF for up to 24 h. HME-coupled 3D printing successfully produced a patient-centric and personalized DSF extended-release vaginal film with a reduced dose and longer dosing interval.

The Effect of Iron Replacement Therapy on HbA1c Levels in Diabetic and Nondiabetic Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have reported that iron-deficiency anemia (IDA) and its treatment might lead to a distorted reading of glycated hemoglobin (HbA1c) value. Hence, this review aims to systematically investigate the effect of iron replacement therapy (IRT) on HbA1c levels, as the literature is deficient in assessing this clinical phenomenon. METHODS: An electronic search of the Cochrane, MEDLINE, and Embase databases was conducted by four independent authors. RESULTS: Among the 8332 articles identified using the search strategy, 10 records (with a total of 2113 participants) met the inclusion criteria and were analyzed. In nine of the studies, IRT was found to decrease HbA1c levels; in the remaining study, IRT was found to increase HbA1c levels. The effect size of the pooled standardized mean difference in HbA1c levels between the treatment and control groups with IDA was 1.8 (95% CI = -0.5, 2.31). Heterogeneity was assessed using the I2 and χ2 tests, and the resultant values were 98.46% and p = 0.09, respectively. Additionally, the mean difference between the HbA1c levels (pre-IRT and post-IRT) showed a drop in the HbA1c levels which ranged from 1.20 to 0.43 mg/dL. CONCLUSIONS: The results suggest that IRT decreases HbA1c levels, and it is helpful in treating IDA patients with poor glycemic control. Accordingly, the results provide an added perspective on antidiabetic medication dosing and physicians' interpretation of initially elevated HbA1c values.

Critical Care Nurses' Knowledge of Tracheostomy Care.

Background: Tracheostomy care is a standard procedure that nurses perform in Critical Care Units (CCUs) to reduce complications from tracheostomy. The literature indicates a clear variety of care and practice in managing tracheostomy patients within the healthcare system. This study was conducted to assess the knowledge level of tracheostomy care among nurses in CCUs in Jordanian hospitals. Materials and Methods: A cross-sectional descriptive design was used for this study. A convenience sample of 260 nurses working in the CCUs of four government hospitals completed a self-reported structured questionnaire. Data were collected from January 2021 to March 2021. A t-test and one-way Analysis of Variance (ANOVA) were used to assess the differences among socio-demographic variables in terms of knowledge score. Results: The result revealed that the level of knowledge was suboptimal. There was a statistically significant difference in the mean level of knowledge regarding tracheostomy care (in all dimensions) by age (F = 22.595, p < 0.001), educational level (F = 355.30, p < 0.001), and work experience (F = 13.63, p < 0.001). For gender, there was a statistically significant difference in knowledge of the tracheostomy suctioning dimension (p = 0.001). Conclusions: The level of knowledge among nurses regarding tracheostomy care was moderate, indicating an urgent need for education.

A comparison of the preemptive effects of oral pregabalin and gabapentin on acute postoperative sedation and complications in patients undergoing lumbar spine surgery.

BACKGROUND: Gabapentinoids are often administered preoperatively, as they have been shown to reduce postoperative opioid consumption and pain scores however sedation has always been a concern because of sedative side effect. OBJECTIVE: This study was intended to compare oral gabapentin versus oral pregabalin sedative effects and complications in patients undergoing lumbar spine surgery under general anaesthesia. METHODS: This study was a true experimental randomised, placebo-controlled, prospective study, conducted at Rafedia Government Surgical Hospital in Nablus, Palestine. The sample consisted of 60 male and female patients undergoing elective lumbar spine surgeries in the department of neurology and aged from 18 to 70 years. The patients were divided into three groups (20 patients each): The pregabalin 150mg group, the gabapentin group and the placebo group. FINDINGS: Nearly 51.7% of the participants reported that they experienced a feeling of nausea or vomiting after the operation. There were statistically significant differences (p-value = 0.008) between the groups in how often complications happen after surgery. CONCLUSIONS: Preemptive pregabalin (150mg) was established to have a more sedative effect and lowered complications than gabapentin (300mg).

Profiling of pharmacogenomic variants in CYP2D6 and DPYD in indigenous Arab breast cancer patients.

Aim: The indigenous Arab population is underrepresented in genomic studies and the landscape of actionable pharmacogenomic variants among Arab breast cancer patients remains unclear. Materials & methods: Exome sequencing was performed on 220 unselected Arab female breast cancer patients and germline variants in CYP2D6 and DPYD were profiled using a deep learning method. Results: In total, 13 (5.9%) patients had clinically actionable results and 56 (25.5%) carried an allele in DYPD or CYP2D6 with unknown impact on drug metabolism. In addition, four unique novel missense variants were discovered, including one in CYP2D6 (p.Arg64Leu) with high predicted pathogenicity. Conclusion: A nontrivial subset of Arab breast cancer patients can potentially benefit from pretreatment molecular profiling, and further study is needed to improve characterization of the pharmacogenomic landscape.