Mitigating Drug Stability Challenges Through Cocrystallization.

Drug stability plays a significant role in the pharmaceutical industry from early-phase drug discovery to product registration as well as the entire life cycle of a product. Various formulation approaches have been employed to overcome drug stability issues. These approaches are sometimes time-consuming which ultimately affect the timeline of the product launch and may further require formulation optimization steps, affecting the overall cost. Pharmaceutical cocrystal is a well-established route to fine tune the biopharmaceutical properties of drugs without covalent modification. This article highlights the role of cocrystallization in mitigating the stability issues of challenging drug molecules. Representative case studies wherein the drug stability issue is addressed through pharmaceutical cocrystals have been discussed briefly and are summarized in tabular form. The emphasis has been made on the structural information of cocrystals and understanding the mechanism that improves the stability of the parent drug through cocrystallization. Besides, a guided strategy has been proposed to modulate the stability of drug molecules through cocrystallization approach. Finally, the stability concern of fixed-dose or drug combinations and the challenges associated with cocrystals are also touched.

Maisotsenko Cycle for Heat Recovery in Gas Turbines: A Fundamental Thermodynamic Assessment.

This paper reports the Maisotsenko's cycle-based waste heat recovery system with enhanced humidification to exploit the maximum waste heat recovery potential of the gas turbine. This research uses an integrated methodology coupling thermodynamic balances with heat transfer model of air saturator. The performance of the system is deduced which are assisted with sensitivity analysis indicating the optimal mass flow rate ratio (0.7-0.8) and pressure ratio (4.5-5.0) between the topping and bottoming cycles, and the air saturator split (extraction) ratio (0.5). The net-work output, energy, and exergy efficiencies of the system are found to be ≈58.39 MW, ≈55.85%, and ≈52.79%, respectively. The maximum exergy destruction ratios are found as 68.2% for the combustion chamber, 16.0% for the topping turbine, 5.7% for topping compressor, 4.9% air saturator. The integration of Maisotsenko's cycle-based waste heat recovery system with a comprehensive thermodynamic model, as demonstrated in this research, offers valuable insights into enhancing the efficiency, cost-effectiveness, and environmental impact of gas turbines. By presenting fundamental equations related to thermodynamic balances, this work serves as an invaluable educational resource, equipping future researchers and students with the knowledge and skills needed to advance the study of thermodynamics and sustainable energy solutions.

Outcome of Post-intubation Tracheal Stenosis (PITS) with Primary Resection and Anastomosis.

OBJECTIVE: To ascertain the outcome of primary resection anastomosis in patients of post-intubation tracheal stenosis (PITS) and the associated morbidity. STUDY DESIGN: A case series. PLACE AND DURATION OF STUDY: Department of Thoracic Surgery, Combined Military Hospital, (CMH) Rawalpindi, Lahore and Multan from January 2010 to August 2018. METHODOLOGY: Patients with tracheal stenosis due to prolonged intubation with functional were included. Exclusion criteria were patients having stenosis due to malignant cause, trauma and glottic stenosis involving vocal cords. Clinical examination, computerised tomography (CT) of neck plus chest and fiberoptic bronchoscopy were done in all the patients, while virtual bronchoscopy were done in 35 cases. Sharp dissection, aided by loupes, was the preferred technique. Thyroid tissue and strap muscle were used as flap for high cricoid lesion. Guardian stitch was applied to all cases. Postoperative elective bronchoscopy was performed after a fortnight. RESULTS: Among 43 patients, [26 (60.5%) men and 17 (39.5) women] 18 patients were intubated for days >10 ,18 for <10 and 7 for <3 days. Thirty-four (79.1%) patients were under 40 years of age, while 23 patients had tracheostomy incorporated in surgery. Bronchoscopy evaluation of distance from vocal cords showed involvement of the first ring in six patients, 1st ring normal in 1, 2 rings normal in 17, while 3 or more rings spared in 19 patients. Length of stenotic segment was <2 cm in 17, between 2-3 cm in 21, and between 3-5 cm in five patients. All patients were successfully extubated. Two patients had twin lesions. Seven patients required hyoid bone excision and release. There was one recurrent stenosis managed successfully with dilatation and granulation removal. CONCLUSION: Post-intubation tracheal stenosis (PITS) is curable disease. Primary resection and anastomosis remain the gold standard with acceptable morbidity and mortality. Key Words: Tracheal stenosis, Intubation, Resection, Primary anastomosis.

Laser Discoloration in Acrylic Painting of Visual Art: Experiment and Modeling.

This study discloses a method for painting artwork using a CO2 laser. The continuous-wave laser beam, at a predetermined heat flux and a predetermined number of laser beam passes, mixes and displaces the plurality of colored polymer-based compositions, respectively, by way of melting and vaporizing them. Experiments showed a great accuracy of colors and designed patterns between the computer aided design (CAD) drawing and what was achieved after laser discoloration. It was found that lower values of power and speed provide sufficient energy and time to make a melt pool of colors and cause their vaporization from the surface. A detailed numerical simulation was performed to obtain a detailed understanding of the physics of laser interaction with paint using ABAQUS software. The comparative analysis indicated that the top layer of paint (including yellow and green colors) melted upon increasing cutting speed and employing one laser pass. For blue and red paints, two passes of lasers are required; in the case of red color, lower laser speed is also necessary to intensify the heat. This method can be applied for making art designs on each surface color because it is based on melting and vaporization using a laser.

Laser-Assisted High Speed Machining of 316 Stainless Steel: The Effect of Water-Soluble Sago Starch Based Cutting Fluid on Surface Roughness and Tool Wear.

Laser-assisted high speed milling is a subtractive machining method that employs a laser to thermally soften a difficult-to-cut material's surface in order to enhance machinability at a high material removal rate with improved surface finish and tool life. However, this machining with high speed leads to high friction between workpiece and tool, and can result in high temperatures, impairing the surface quality. Use of conventional cutting fluid may not effectively control the heat generation. Besides, vegetable-based cutting fluids are invariably a major source of food insecurity of edible oils which is traditionally used as a staple food in many countries. Thus, the primary objective of this study is to experimentally investigate the effects of water-soluble sago starch-based cutting fluid on surface roughness and tool's flank wear using response surface methodology (RSM) while machining of 316 stainless steel. In order to observe the comparison, the experiments with same machining parameters are conducted with conventional cutting fluid. The prepared water-soluble sago starch based cutting fluid showed excellent cooling and lubricating performance. Therefore, in comparison to the machining using conventional cutting fluid, a decrease of 48.23% in surface roughness and 38.41% in flank wear were noted using presented approach. Furthermore, using the extreme learning machine (ELM), the obtained data is modeled to predict surface roughness and flank wear and showed good agreement between observations and predictions.

Efficacy Of Prophylactic Antibiotics In Reducing Posttonsillectomy Haemorrhage.

BACKGROUND: This study aims toward establishing the impact of prophylactic pre-operative antimicrobial therapy on tonsillectomy related haemorrhage. METHODS: In this randomized controlled trial conducted at Combined Military Hospital, Abbottabad from January 2017 till August 2019, 121 children and adult patients who had consented and had undergone tonsillectomy were evaluated for procedure related haemorrhage. RESULTS: Incidence rate of secondary posttonsillectomy haemorrhage and need for re-hospitalization was significantly less in patients who had completed pre-operative prophylactic antibiotics. Patient-reported secondary haemorrhage was recorded in 4.59% (n=9) cases who did not receive pre-operative antibiotic prophylaxis, thereby increasing morbidity and prolonging hospital stay. Secondary post-operative bleeding only occurred in 1.18% (n=2) patients who received appropriate pre-operative anti-microbial prophylaxis. CONCLUSIONS: We strongly imply that prophylactic pre-operative antibiotics reduce procedure related complications in all patients undergoing tonsillectomy.

Synthesis of Functional Silver Nanoparticles and Microparticles with Modifiers and Evaluation of Their Antimicrobial, Anticancer, and Antioxidant Activity.

An accumulating body of evidence reports the synthesis and biomedical applications of silver nanoparticles. However, the studies regarding the use of maleic acid and citric acid in the synthesis of nano-sized silver particles (AgNPs) and micro-sized silver particles (AgMPs) as well as their antibacterial, antifungal, and anticancer activities have not been reported. In the current study, we synthesized AgNPs and AgMPs using maleic acid and citric acid as capping agents and have characterized them by UV-Vis, energy-dispersive X-Ray spectroscopy (EDS), X-Ray diffraction (XRD), and scanning electron microscope (SEM) analysis. The capped silver particles were examined for their antimicrobial activity and cytotoxicity against bacteria, fungi, and brine shrimp. Additionally, the anticancer activity of these particles was tested against human breast and liver cancer cell lines. The free radical scavenging activity of capped silver particles was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. SEM analysis revealed a round plate-like morphology of maleic acid capped particles with an average size of 39 ± 4 nm, whereas citric acid capped particles display flower-shaped morphology with rough surfaces and an average size of 250 ± 5 nm. The uncapped AgMPs were hexagonal with 500 ± 4 nm size. EDS and XRD analysis confirmed the presence of Ag and face-centered cubic crystalline nature, respectively. Functionally, capped silver particles exhibited antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus) and Gram-negative bacteria (Salmonella setubal, Enterobacter aerogenes, and Agrobacterium tumefaciens). The bactericidal activity was more active against Gram-negative bacteria with minimum inhibitory concentration (MIC) as low as 5 ppm as compared to 25 ppm for Gram-positive. Similarly, the silver particles demonstrated antifungal activity by inhibiting the growth of five fungal strains (Mucor species, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, and Fusarium solani) up to 50% at the concentration of 500 ppm. Additionally, these particles showed substantial toxicity against brine shrimp and also significantly inhibited the proliferation of breast cancer (MCF7) and liver cancer (HePG2) cell lines (IC50 8.9-18.56 µM). Uncapped AgMPs were less effective, inhibiting only the proliferation of MCF7 cells with IC50 46.54 µM. Besides cytotoxicity, these particles acted as potential antioxidants, showing free radical scavenging up to 74.4% in a concentration-dependent manner. Taken together, our results showed that the modifiers affect the shape and size of silver particles and may, in part, contribute to the antimicrobial and antioxidant activity of silver particles. However, the contribution of maleic acid and citric acid in enhancing the antimicrobial, anticancer, and antioxidant potential independent of silver nano and microparticles needs to be studied further. In vivo experiments may determine the therapeutic effectiveness of silver particles capped with these modifiers.

Diverse Anatomical Configuration Of Recurrent Laryngeal Nerve In Relation To Inferior Thyroid Artery, An Experience With 51 Thyroidectomies.

BACKGROUND: Objective of the study is to elaborate the anatomical variants of recurrent laryngeal nerve in relation to inferior thyroid artery, encountered during thyroidectomy operation. It is descriptive, case series, conducted at the Department of Ear Nose & Throat, Combined Military Hospital, Abbottabad. The study was conducted from January 2016 to September 2017. METHODS: Fifty-one patients underwent extra-capsular thyroidectomy in general anaesthesia. The dissection was carried out in a standard way in all patients. Recurrent laryngeal nerves were identified and exposed in every patient, and their anatomical relations were recorded in database. RESULTS: Recurrent laryngeal nerve was seen over riding the ramification of inferior thyroid artery in majority of left sided dissected specimen, however on the right side the principal nerve was found to be ascending through the branches of inferior thyroid artery.. CONCLUSIONS: Iatrogenic vocal cord paralysis has sinister implication on quality of life of the patient undergoing thyroidectomy. Anatomic variants of recurrent laryngeal nerve are well known and frequent. The disastrous outcome of inadvertent recurrent laryngeal nerve trauma can be adequately prevented by thoroughly knowing its anatomical variants, and intra-operatively identifying and exposing the principal nerves.

Ectopic Warthin's Tumour Masquerading As Infected Branchial Cyst.

Salivary gland tumours are relatively uncommon but they present globally regardless of age. Most of these tumours are benign and involve the parotid gland. Though strictly confined to the parotid gland, Warthin's tumours can exceptionally present at an ectopic site of head and neck. Of particular significance is its striking similarity with a lymph node, an inclusion cyst, branchial cyst or a malignant mass, especially when it presents in the upper cervical region.

Forgotten Post Operative Nasal Splint & Oro-Nasal Fistula.

of the oral cavity. It may develop as a congenital defect e.g. cleft palate, or rarely, consequent to an operative procedure like a sub muco-perichondrial resection surgery of the nasal septum. After nasal septal corrective surgery, follow up of the patient with meticulous nasal toilet and detailed examination is mandatory. In operated patients who do not report to follow up, and later on present with persisting nasal discharge, pain, nasal blockage and exsanguination must alert a clinician for any evidence of a possibly retained foreign object. Inadvertently retained nasal splints can cause long lasting morbidity due to a possible chronic sinusitis, toxic shock syndrome and palatal perforation.

Pulmonary complications associated with head and neck cancer surgery.

OBJECTIVE: To evaluate the frequency of short-term pulmonary complications in the patients undergoing various head and neck cancer surgeries in our setup and to assess possible risk factors responsible for these complications. STUDY DESIGN: Quasi experimental study. PLACE AND DURATION OF STUDY: Department of ENT, Head and Neck Surgery, Combined Military Hospital, Rawalpindi from July 2005 till August 2006. PATIENTS AND METHODS: Seventy patients of age group 20 to 80 years, regardless of gender, treated surgically for head and neck cancers were enrolled. Main outcome measures included development of pulmonary complications following 15 days of oncological surgery. The complications studied were pneumothorax, bronchopneumonia, atelectasis, pulmonary embolism and cardiopulmonary arrest. RESULTS: A total of 24.28% patients suffered from postoperative pulmonary complications; 17.14% developed bronchopneumonia, 5.71% pulmonary embolism, and 1.42% went into cardiopulmonary arrest, none developed pneumothorax or pulmonary atelectasis. A significant correlation of postoperative bronchopneumonia was seen with heavy smoking and assisted ventilation. Pulmonary embolism was associated with extended assisted ventilation and prolonged surgery. Cardiopulmonary arrest was associated with comorbidity and assisted ventilation after surgery. CONCLUSION: The frequency of bronchopneumonia supersedes all of the postoperative pulmonary complications in head and neck oncological surgery. Patients at risk of developing postoperative complications are heavy smokers, diabetics, those undergoing prolonged surgery, tracheostomy, and extended assisted ventilation.

Microbiological Profile From Middle Ear And Nasopharynx In Patients Suffering From Chronic Active Mucosal Otitis Media.

BACKGROUND: Chronic otitis media is described as a tympanic membrane perforation and ear discharge for more than six weeks duration. Ascending infection from the nasopharynx into the middle ear cleft has been attributed to prevent resolution of chronic otitis media. This research aims to determine the association between the microbiological flora of the nasopharynx with that of the middle ear in patients suffering from chronic (active) mucosal otitis media.. METHODS: Our study is a hospital-based cross-sectional survey. It was conducted from December 2015 to February 2017 at the Department of ENT, Combined Military Hospital, Abbottabad. Ear and nasopharyngeal swabs were obtained from 65 patients of chronic active mucosal otitis media and sent for microbiological analysis. Microbiological culture and sensitivity test was performed to identify the microbial spectrum of each specimen. Performa bearing the result of otoscopy, aspirate and swabs were completed for middle ear and the nasopharyngeal culture with reference to each patient. Descriptive statistics and Pearson's chi square analysis were performed using SPSS-22. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa are foremost microorganisms found in otorrhea culture isolated from patients of chronic active mucosal otitis media. Majority of the cultures from nasopharynx of these patients did not reveal any growth after incubation for 48 hours. CONCLUSIONS: A statistically insignificant association exists between the microbiological spectrum of the middle ear and the nasopharynx of patients suffering from chronic active mucosal otitis media. Micro organisms' exposure from a perforated tympanic membrane remains leading cause of persistent otorrhea, rather than ascending infection through the Eustachian tube.