Controlled Sublimation Rate of Guest Drug from Polymorphic Forms of a Cyclodextrin-Based Polypseudorotaxane Complex and Its Correlation with Molecular Dynamics as Probed by Solid-State NMR.

Encapsulation of active pharmaceutical ingredients (APIs) in confined spaces has been extensively explored as it dramatically alters the molecular dynamics and physical properties of the API. Herein, we explored the effect of encapsulation on the molecular dynamics and physical stability of a guest drug, salicylic acid (SA), confined in the intermolecular spaces of γ-cyclodextrin (γ-CD) and poly(ethylene glycol) (PEG)-based polypseudorotaxane (PPRX) structure. The sublimation tendency of SA encapsulated in three polymorphic forms of the γ-CD/PEG-based PPRX complex, monoclinic columnar (MC), hexagonal columnar (HC), and tetragonal columnar (TC), was investigated. The SA sublimation rate was decreased by 3.0-6.6-fold and varied in the order of MC form > HC form > TC form complex. The 13C and 1H magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectra and 13C spin-lattice relaxation time (T1) indicated that the encapsulated SA molecules existed as the monomeric form, and its molecular mobility increased in the order of MC form > HC form > TC form complex. In the complexes, a rapid chemical exchange between two dynamic states of SA (free and bound) was suggested, with varying adsorption/desorption rates accounting for its distinct molecular mobility. This adsorption/desorption process was influenced by proton exchange at the interaction site and interaction strength of SA in the complexes, as evidenced by 1H MAS spectra and temperature dependency of the 13C carbonyl chemical shift. A positive correlation between the molecular mobility of SA and its sublimation rate was established. Moreover, the molecular mobility of γ-CD and PEG in the complexes coincided with that of SA, which can be explained by fast guest-driven dynamics. This is the first report on the stability improvement of an API through complexation in polymorphic supramolecular host structures. The relationship between the molecular dynamics and physical properties of encapsulated API will aid in the rational design of drug delivery systems.

Evaluation of neck-circumference- thyromental- distance ratio as a predictor of difficult intubation: A prospective, observational study.

Background and Aims: Preoperative identification of difficult airway and subsequent planning is of utmost importance for a patient's safety. Previous studies have identified the ratio of the neck circumference (NC) to the thyromental distance (TMD); NC/TMD as a reliable predictor of difficult intubation in obese patients. But there is a lack of studies evaluating the NC/TMD in non-obese patients. Therefore, the aim of this study was to compare the NC/TMD as a predictor of difficult intubation in both obese and non-obese patients. Methods: A prospective, observational study was conducted after obtaining institutional ethics committee clearance and written and informed consent from each patient. One hundred adult patients undergoing elective surgeries under general anaesthesia with orotracheal intubation were included in this study. Difficulty in intubation was assessed using the Intubation Difficulty Scale. The NC/TMD was calculated and the predictive accuracy of NC/TMD and other established parameters in obese and non-obese patients were compared. Results: Univariate logistic regression analysis showed that gender, weight, body mass index, inter-incisor gap, Mallampati classification, NC, TMD, sternomental distance, and NC/TMD had a significant association with difficult intubation. NC/TMD has a higher sensitivity, specificity, and positive and negative predictive value with better predictability in comparison to other parameters. Conclusion: The NC/TMD is a reliable and better predictor of difficult intubation in both obese and non-obese patients in comparison to NC, TMD, and sternomental distance alone.

Isomorphism: 'molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid.

The non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and tolfenamic acid (TFA) have a close resemblance in their molecular scaffold, whereby a methyl group in MFA is substituted by a chloro group in TFA. The present study demonstrates the isomorphous nature of these compounds in a series of their multicomponent solids. Furthermore, the unique nature of MFA and TFA has been demonstrated while excavating their alternate solid forms in that, by varying the drug (MFA or TFA) to coformer [4-di-methyl-amino-pyridine (DMAP)] stoichiometric ratio, both drugs have produced three different types of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate (1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close similarity of TFA and MFA structures, these multicomponent solids have shown an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their similarity in terms of space group and structural packing with isomorphic nature among the pairs. Herein, the experimental results are generalized in a broader perspective for predictably identifying any possible new forms of comparable compounds by mapping their crystal structure landscapes. The utility of such an approach is evident from the identification of polymorph VI of TFA from hetero-seeding with isomorphous MFA form I from acetone-methanol (1:1) solution. That aside, a pseudopolymorph of TFA with di-methyl-formamide (DMF) was obtained, which also has some structural similarity to that of the solvate MFA:DMF. These new isostructural pairs are discussed in the context of solid form screening using structural landscape similarity.

Unilateral versus bilateral spinal anaesthesia in geriatric patients undergoing hemiarthroplasty: a comparative study.

INTRODUCTION: Conventional bilateral spinal anaesthesia can produce haemodynamic alterations that can be detrimental to geriatric patients. Unilateral spinal anaesthesia produces predominant blockade on the operated side, thereby reducing the incidence of hypotension. There is a scarcity of comparative studies evaluating the effects of unilateral spinal anaesthesia in the elderly population. Therefore, we conducted this study to compare the effects of unilateral and bilateral spinal anaesthesia in geriatric patients. MATERIAL AND METHODS: A prospective, parallel group, randomized, controlled study was conducted on 72 patients of age 60-85 years, ASA physical status I and II undergoing hemiarthroplasty under spinal anaesthesia. Patients were randomly allocated to two groups: patients in group U (n = 36) received unilateral spinal anaesthesia, those in group B (n = 36) received bilateral spinal anaesthesia. All patients received 1.5 mL of hyperbaric bupivacaine (0.5%) and 0.5 mL of fentanyl intrathecally in the lateral decubitus position. Patients in group B were turned to the supine position and those in group U maintained the lateral decubitus position for 15 minutes. Intraoperative and postoperative haemodynamic parameters, Bromage score and sensory block height were compared. RESULTS: Hypotension in group B patient was more pronounced compared to group U. There was no significant difference in the Bromage score and the number of patients reaching T10 sensory block height on the operated side between the two groups. The Bromage score and the number of patients reaching T10 sensory block height on the non-operated side were higher in group B. CONCLUSIONS: In geriatric patients unilateral spinal anaesthesia produces predominant motor and sensory block on the operated side with less hypotension.

Comparison between Macintosh, Miller and McCoy laryngoscope blade size 2 in paediatric patients - A randomised controlled trial.

BACKGROUND AND AIMS: Paediatric airway needs special consideration as it is not a miniature replica of adult airway, rather it has different anatomy with different proportion and angulations. This study was conducted with the aim to find a laryngoscope blade that provides best laryngoscopic and intubation conditions in paediatric patients of age 2-6 years. METHODS: This trial was conducted in a total of 75 children age 2-6 years, either gender, with American Society of Anesthesiologists grade I or II scheduled for elective surgery under general anaesthesia. They were randomly allocated to groups A, B and C to be intubated with Macintosh, Miller and McCoy blades, respectively. Intubation Difficulty Score (IDS) was considered as primary outcome, and Cormack-Lehane grade and Percentage of Glottic Opening (POGO) score were taken as secondary outcome. Data were compared by ANOVA or Kruskal-Wallis or chi square test using Statistica, SPSS and GraphPad Prism softwares. P < 0.05 was considered statistically significant. RESULTS: IDS score was significantly lower (P = 0.002) in group B (0.6 ± 0.7) as compared to group A (1.4 ± 0.9) and group C (1.3 ± 1.1); majority of patients in group B (48%) had Cormack-Lehane grade Ι (P = 0.002) unlike group A (0%) and group C (20%) and POGO score (P < 0.001) was higher in group B (86 ± 23.4) when compared with groups A (68.2 ± 20.5) and C (59.8 ± 28.9). Haemodynamic changes and other intubation parameters were comparable among the groups. CONCLUSION: Miller blade may be considered superior to Macintosh and McCoy blades in terms of glottic visualisation and ease of intubation in paediatric patients.

Enhanced Solubility of Telmisartan Phthalic Acid Cocrystals within the pH Range of a Systemic Absorption Site.

Telmisartan (TLM), a nonpeptide angiotensin II antagonist, is widely prescribed for treating arterial hypertension and marketed by the innovator with the trade name of Micardis and Micardis plus. Telmisartan exhibits low aqueous solubility in the pH range of 3-7, which is the physiological pH. For addressing the issue of poor solubility of TLM, its commercial form makes use of inorganic alkalinizers. The present work illustrates the attempt to improve the solubility of telmisartan via a crystal engineering approach. A novel solid form of telmisartan with phthalic acid was obtained through the solution crystallization method (TPS) and the reaction crystallization method (TPR). Both the forms (TPS and TPR) were thoroughly characterized by powder diffraction X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and 1H NMR and were identified to be two different crystalline forms. Solubility studies of TPS and TPR were conducted at varying pH of phosphate buffer, and they exhibited 11-fold and 22-fold increased solubility, respectively, when compared to that of the pure drug at pH 5, which is within the pH of small intestine at which telmisartan is best absorbed orally from the systemic circulation.

Subclinical hypothyroidism in pregnancy: An emerging problem in Southern West Bengal: A cross-sectional study.

BACKGROUND: Prevalence of subclinical hypothyroidism (SCH) in pregnancy varies widely in different parts of our country, but it has multiple adverse outcomes in both the mother and fetus. OBJECTIVES: This study was conducted to evaluate the prevalence of SCH in pregnant women during the first trimester and to identify the prevalence of thyroid autoimmunity in pregnant women. MATERIALS AND METHODS: This cross-sectional study (March 2014 to February 2015) was conducted among the pregnant women attending antenatal clinic in their first trimester at a tertiary care center. Morning samples of study participants were analyzed for free thyroxin (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab). Data expressed as mean ± standard deviation and percentage (%) as applicable. RESULTS: Of the 510 subjects, 168 had TSH value >2.5 µIU/ml (32.94%) with normal FT4 and they were diagnosed as SCH. TSH level >4.5 µIU/ml was estimated in 13.92% (71) of the subjects. TPO Ab was positive in 57 (33.93%) of subclinical hypothyroid and 5 (1.47%) of normal subjects. 70.42% (50) of the subjects with TSH >4.5 µIU/ml had positive TPO Ab. CONCLUSIONS: Prevalence of SCH is high in South Bengal and routine thyroid screening at the first antenatal visit should be done to reduce the social and financial burden caused by SCH.

Pediatric patient with Bombay blood group: A rare case report.

Bombay blood group is a rare blood group in which there is the absence of H antigen and presence of anti-H antibodies. At the time of blood grouping, this blood group mimics O blood group due to the absence of H antigen, but it shows incompatibility with O group blood during cross matching. Serum grouping or reverse grouping are essential for confirmation of the diagnosis. Patients carrying this blood group can receive blood only from a person with this blood group. Reported cases of anesthesia in the pediatric patient with Bombay blood group are relatively rare. Here, we present successful anesthetic management along with intraoperative blood transfusion in a pediatric patient with Bombay blood group posted for ovarian cystectomy.

Anaphylaxis from atracurium without skin manifestation.

Anaphylaxis is an acute, potentially fatal allergic reaction involving multi organ system that is triggered by a wide range of antigens with a subsequent release of chemical mediators from mast cells and basophils. Diagnosis is primarily clinical though laboratory studies are helpful in further confirmation. Anaphylactic reactions during anesthesia are rare, but can be fatal if not promptly recognized and treated. Among all drugs commonly used in anesthesia, muscle relaxants are the most notorious to trigger anaphylactic reactions and benzylisoquinolinium group of drugs are known to be less common an offender than the steroidal compounds. We report severe anaphylactic reaction after administration of atracurium that was promptly diagnosed and managed without any further morbidity.

A comparison between volume-controlled ventilation and pressure-controlled ventilation in providing better oxygenation in obese patients undergoing laparoscopic cholecystectomy.

BACKGROUND: The maintenance of oxygenation is a commonly encountered problem in obese patients undergoing laparoscopic cholecystectomy. There is no specific guideline on the ventilation modes for this group of patients. Although several studies have been performed to determine the optimal ventilatory settings in these patients, the answer is yet to be found. The aim of this study was to evaluate the efficacy of pressure-controlled ventilation (PCV) in comparison with volume-controlled ventilation (VCV) for maintaining oxygenation during laparoscopic cholecystectomy in obese patients. METHODS: One hundred and two adult patients of ASA physical status I and II, Body Mass Index of 30-40 kg/m(2), scheduled for laparoscopic cholecystectomy were included in this prospective randomized open-label parallel group study. To start with, all patients received VCV. Fifteen minutes after creation of pneumoperitoneum, they were randomized to receive either VCV (Group V) or PCV (Group P). The ventilatory parameters were adjusted accordingly to maintain the end-tidal CO(2) between 35 and 40 mmHg. Respiratory rate, tidal volume, minute ventilation and peak airway pressure were noted. Arterial blood gas analyses were done 15 min after creation of pneumoperitoneum and at 20-min intervals thereafter till the end of the surgery. All data were analysed statistically. RESULTS: Patients in Group P showed a statistically significant (P < 0.05) higher level of PaO(2) and lower value of PAO(2)-PaO(2) than those in Group V. CONCLUSION: PCV is a more effective mode of ventilation in comparison with VCV regarding oxygenation in obese patients undergoing laparoscopic cholecystectomy.

Effect of magnesium infusion on thoracic epidural analgesia.

INTRODUCTION: Patients of lung volume reduction surgery (LVRS) having an ASA status III or more are likely to be further downgraded by surgery to critical levels of pulmonary function. AIM: To compare the efficacy of thoracic epidural block with (0.125%) bupivacaine, fentanyl combination and (0.125%) bupivacaine, fentanyl combination with adjunctive intravenous magnesium infusion for the relief of postoperative pain in patients undergoing LVRS. METHODS: Patients were operated under general anesthesia. Thirty minutes before the anticipated completion of skin closure in both groups, (Group A and Group B) 7 ml of (0.125%) bupivacaine calculated as 1.5 ml/thoracic segment space for achieving analgesia in dermatomes of T4, T5, T6, T7, and T8 segments, along with fentanyl 50 µg (0.5 ml), was administered through the catheter, activating the epidural block, and the time was noted. Thereafter, in patients of Group A, magnesium sulfate injection 30 mg/kg i.v. bolus was followed by infusion of magnesium sulfate at 10 mg/kg/hr and continued up to 24 hours. Group B was treated as control. RESULTS AND ANALYSIS: A significant increase in the mean and maximum duration of analgesia in Group A in comparison with Group B (P<0.05) was observed. Total epidural dose of fentanyl and bupivacaine required in Group A was significantly lower in comparison with Group B in 24 hours. DISCUSSION: Requirement of total doses of local anesthetics along with opioids could be minimized by magnesium infusion; therefore, the further downgradation of patients of LVRS may be prevented. CONCLUSION: Intravenous magnesium can prolong opioid-induced analgesia while minimizing nausea, pruritus, and somnolence.

Controlled transient respiratory arrest along with rapid right ventricular pacing for improving balloon stability during balloon valvuloplasty in pediatric patients with congenital aortic stenosis--a retrospective case series analysis.

Rapid right ventricular pacing is safe, effective, and established method to provide balloon stability during balloon aortic valvuloplasty (BAV). Controlled transient respiratory arrest at this point of time may further reduce left ventricular stroke volume, providing an additional benefit to maintain balloon stability. Two groups were studied. Among the 10 patients, five had rapid pacing alone (Group A), while the other five were provided with cessation of positive pressure breathing as well (Group B). The outcomes of BAV in the two groups of patients were studied. One patient in Group A had failed balloon dilatation even after the fourth attempt, while in Group B there were no failures. The peak systolic gradient reduction was higher in Group B (70.05% in comparison to 52.16% of group A). In Group A, five subjects developed aortic regurgitation (grade 2 in four and grade 3 in one, while no grade 3 aortic regurgitation developed in any patient in Group B). Controlled transient respiratory arrest along with rapid ventricular pacing may be effective in maintaining balloon stability and improve the outcome of BAV.