Application of through-vial impedance spectroscopy as a novel process analytical technology for freeze drying

This study aims to validate and develop applications for a novel impedance-based process analytical technology for monitoring the attributes of the product during the entire freeze-drying process (from pre-freezing and annealing to primary and then secondary drying). This measurement approach involves the application of foil electrodes, mounted externally to a conventional glass freeze-drying vial, and coupled to a high-impedance analyser. The location of the electrodes on the outside, rather than the inside of the vial, leads to a description of the technology as a through-vial impedance spectroscopy (TV-IS) technique. The principle observation from this approach is the interfacial-polarization process arising from the composite impedance of the glass wall and product interface. For a conventional glass vial (of wall thickness ~ 1 mm and cross sectional diameter ~ 22 mm) it was shown that the process is manifest within the frequency range 101 to 106 Hz, as a single, broad band peak which spans 2-3 decades of the imaginary part spectrum. Features of the interfacial-relaxation process, characterised by the peak amplitude, C″Peak, and peak frequency, fpeak, of the imaginary capacitance spectra and the equivalent circuit elements that model the impedance spectra (i.e. the solution resistance (R) and solution capacitance (C) were monitored along with the product temperature data during the cycle(s), for a variety of surrogate formulations comprising lactose, sucrose, mannitol or maltodextrin solutions, during the freezing, re-heating, annealing and primary drying stages of freeze drying. It was shown that the parameters, fpeak and R, are strongly coupled to each other and change as a function of the temperature of the solution and its phase state, whereas C″Peak is strongly coupled to the amount of ice that remains during the drying process. Both log fpeak and log R have a linear dependence on the temperature of the solution, provided there was no phase change in the solution. The crystallization process (ice onset, solidification and equilibration to shelf temperature) is characterized well by both log fpeak and log R, whereas the parameter R demonstrates most clearly the formation of eutectic crystallization during freezing. In contrast it was the parameter C which was most sensitive to the detection of the glass transition during re-heating. During primary drying, it was shown that C″peak, is dependent on the amount of ice remaining and therefore provides a convenient assessment of the rate of drying and primary drying end point. The impedance changes during annealing provide a mechanistic basis for the modifications in ice structure which result directly in the observed decrease in primary drying times. The principal observation on annealing of a 10% w/v solution of maltodextrin, was the minimal changes in the glass transition (recorded at ~−16 °C) during the re-heating and cooling step (post-annealing). This result alone appears to indicate that a maximum freeze concentration was achieved during first freezing with no further ice being formed on annealing. The phenomenon of devitrification (and the production of more ice, and hence larger ice crystals) was therefore discounted as the mechanism by which annealing impacts the drying time. Having excluded devitrification from the mechanism of annealing enhanced drying, it was then possible to conclude that the decrease in the electrical resistance (that was observed during the annealing hold time) must necessarily result from the simplified structure of the unfrozen fraction and the improved connectivity of ice crystals that may be the consequence of Ostwald ripening. The application of through vial impedance measurement approach provides a non-invasive, real time monitoring of critical process parameters which subsequently leads to an improved understanding of the mechanisms and effects of different parameters, providing a reliable basis for process optimization, along with improved risk management to ensure optimum quality of the formulation and optimization of the freeze drying process

Frequency of Thyroid Dysfunction and Congenital Heart Defects in Subjects with Down Syndrome

ABSTRACT: Background: Down syndrome (DS) is the most common chromosomal abnormality with prevalence of 1 in 700-1500 live births. Its manifestations may include congenital heart defects(CHD), thyroid dysfunctions, hematopoietic disorders, early-onset Alzheimer disease, gastrointestinal disorders, neuromuscular weakness, hearing and visual problems, characteristic facial and physical features. The prevalence of thyroid disorders and congenital heart diseases are higher in DS patients than in general population. Objective:To explore the frequency, and types of congenital heart defects (CHD) and Thyroid disorders in children with Down syndrome (DS) in the children hospital and the institute of child health (CHICH) Multan. Study design:  Descriptive cross sectional Setting: Outpatient department (OPD) of CHICH Multan Method:A total of 158 down syndrome (DS) patients of 0 to 15 years of age, of both genders were included in this study from October 2019 to October 2020. DS was diagnosed by specific clinical features and karyotyping. Age, sex and mother’s age was noted. Blood samples of all the patients were sent for karyotyping and serum T4 and Thyroid stimulation hormone (TSH). For patients more than 36 months, blood samples were also sent for Antithyroglobulin and antithyroid peroxidase antibodies. Echocardiography of all the patients was done. Data was collected and analyzed by using SPSS version 16.0. Results:Out of 158 DS children most presented below 6months of age, with male to female ratio of 1:1.4. Mostly mothers were between 20 to 40 years of age. Karyotyping revealed non disjunction in 97% of cases. Cardiac abnormalities were found in 48% of DS children. Most common Type was VSD (10.9%), Thyroid abnormalities were detected in 24% of DS patients, subclinical hypothyroidism (13.9%) was most common. Conclusion: CHD and Thyroid disorders must be ruled out in all DS patients,to start early management.  Keywords: Down syndrome, Congenital heart disease, hypothyroidism

Formulation Optimization and In-vitro Evaluation of Oral Floating Captopril Matrix Tablets using Factorial Design

Purpose: To develop a zero-order sustained release floating formulation of captopril, and optimize its drug release for enhanced oral bioavailability.Methods: A relatively new approach, 32 full factorial design, was used to formulate floating captopril matrix tablets and to systematically optimize its drug release using varying levels of xanthan gum and hydroxypropyl methylcellulose (HPMC) K100M polymers. Calcium carbonate was used as gasgenerating agent. After setting the levels by preliminary trials, nine tablet formulations (F1 - F9) were prepared by wet granulation method using Design Expert Software® - suggested combinations of polymers. The concentrations of HPMC K100M (X1) and xanthan gum (X2) were chosen as control variables. Conversely, the response variables selected were timed to release 50 % of the drug (t50%) at 6 h (Q6) and 12 h (Q12). Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to assess compatibility between the drug and the excipients. The validity of the developed mathematical equations was assessed by designing three extra check-points.Results: The response surface plots drawn demonstrated the suitability of the hydrophilic matrixforming agents for formulating controlled release floating tablets of captopril. FTIR and DSC spectra showed no noticeable incompatibility between drug and polymers in both physical mixtures and in formulations. Floating time lag remained < 5.5 min with floating duration > 12 h. Considerable agreement was observed between predicted and actual release parameters. Fitting the data into different kinetic models showed that non-Fickian behavior for diffusion exponent (n) differed from 0.588 and 0.811.Conclusion: Optimum formulation (F4) showed satisfactory release profile. Moreover, the study successfully demonstrated influence of polymer blends in controlling release variables.Keywords: Captopril, Xanthan gum, Hydroxy propyl methyl cellulose , Factorial design, Bioavailabilit

An Insight into Different Strategies for Control and Prophylaxis of Fasciolosis: A Review

Fasciolosis is one of the important diseases of livestock and has zoonotic importance. Fasciolosis can cause huge economic losses due to decrease in milk and meat production, decreased feed conversion ratio, and cost of treatment. Treatment and prophylaxis strategies for Fasciola infection are formed based on epidemiological data. The control of Fasciola infection can be attained by treating the animals with active anthelmintics. The use of different combinations of anthelmintics with a possible rotation is more effective against immature as well as adult flukes. Control of the intermediate host (snail) is vital for the reduction of fasciolosis. Due to the rapid growth of snails, the eradication is quite difficult in waterlogged and marshy areas. The use of different grazing methods and treatment of grazing areas can also help to control fasciolosis. A variety of antigens generated by Fasciola spp. have been shown to protect against liver fluke infection. The crude antigens, excretory/secretory, and refined antigens and their combination can be used as prophylactic treatment for the control of fasciolosis. The use of any of the single or combination of these methods can be very effective for the control of fasciolosis

STOCK MARKET COINTEGRATION: EVIDENCE FROM DEVELOPED AND DEVELOPING EQUITY MARKETS

This study examined the relationship between KSE and stockmarkets of developed and developing countries for the period of 2000-2012. Cointegration approach showed that one cointegrationequation exists in KSE and developed countries equity markets andtwo cointegration equations exist in KSE and developing countriesequity markets case. Granger causality test showed a uni-directionalrelationship between KSE and developed and developing markets,and a bi-directional relationship with Taiwan’s equity market.Variance decomposition analysis showed that most of the changes inKSE are due to its own dynamics in both the developed and developingmarkets. Correlation matrix shows that there is a weak or nocorrelation between the KSE and developed and developing countriesso the benefit of diversification can be achieved by investing in KSE

Chattering Free Sliding Mode Control and State Dependent Kalman Filter Design for Underground Gasification Energy Conversion Process

The fluctuations in the heating value of an underground coal gasification (UCG) process limit its application in electricity generation, where a desired composition of the combustible gases is required to operate gas turbines efficiently. This shortcoming can be addressed by designing a robust control scheme for the process. In the current research work, a model-based, chattering-free sliding mode control (CFSMC) algorithm is developed to maintain a desired heating value trajectory of the syngas mixture. Besides robustness, CFSMC yields reduced chattering due to continuous control law, and the tracking error also converges in finite time. To estimate the unmeasurable states required for the controller synthesis, a state-dependent Kalman filter (SDKF) based on the quasi-linear decomposition of the nonlinear model is employed. The simulation results demonstrate that despite the external disturbance and measurement noise, the control methodology yields good tracking performance. A comparative analysis is also made between CFSMC, a conventional SMC, and an already designed dynamic integral SMC (DISMC), which shows that CFSMC yields (Formula presented.) and (Formula presented.) improvement in the root mean squared tracking error with respect to SMC and DISMC, respectively. Moreover, CFSMC consumes (Formula presented.) and (Formula presented.) less control energy as compared to SMC and DISMC, respectively

Development and validation of a spectroscopic method for the simultaneous analysis of miconazole nitrate and hydrocortisone acetate in pharmaceutical dosage form

Purpose: To develop a new analytical method for the quantitative analysis of miconazole nitrate (MCN) and hydrocortisone (HCA) in pharmaceutical creams.Methods: The study was accomplished in three steps. In the first stage, a spectroscopic method was developed for the simultaneous analysis of miconazole (MCN) and hydrocortisone (HCA). For this purpose, serial dilutions of both drugs were prepared using ethanol: water (50:50) as the solvent system. All solutions were analyzed for absorbance spectrophotometrically at 205 and 249 nm for MCN and HCA, respectively. The method was validated for linearity, range, accuracy, precision and robustness. A commercial formulation was also assayed by the proposed method.Results: The absorbance data were linear over a concentration range of 1 to 12 μg/mL for MCN and 1 to 40 μg/mL for HCA, with correlation coefficient of 0.9995 and 0.9984, respectively. Limit of detection (LOD) and of quantification (LOQ) of MCN were  0.49 and 1.49 μg/mL, respectively, and for HCA, 1.50 and 4.57 μg/mL, respectively. The assay results for the commercial  formulation were within the limits specified in British Pharmacopoeia.Conclusion: Simultaneous quantification of miconazole (MCN) and hydrocortisone (HCA) by UV spectroscopy provides a simple, reliable and robust method for the characterization of a mixture of the drugs in a dosage form.Keywords: Simultaneous analysis, Miconazole nitrate, Hdrocortisone acetate, UV-visible spectroscopy, Method validatio

Issues in Transformation from Conventional Banking to Islamic Banking

The present era has witnessed intensive changes in last few decades. The transformation of conventional financial system to Islamic financial system is one of these drastic changes the world has faced. Islamic banking is the major constituent of the Islamic finance. In line with these transformations, Islamic banks and financial institutions are facing several problems due to non-existence of comprehensive framework. However, some prominent issues are convergence issues, stability and regulatory issues, existence of different schools of thought and sensitivity towards role of religion in commercial and financial sector. A careful analysis of these issues can lead to sort out the solutions. The approach to overcome these challenges will determine the future success or failure of the industry. Therefore, this study shed a light on some major challenges that can hinder the progress and benefits of Islamic finance promises. Keywords: Islamic Banks, Regulatory Framework, Financial Regulation, Governance, Financial Stability, Risk Management JEL Classifications: G21, G28, G32, O16, P1

Hydroxypropyl cellulose-based orally disintegrating films of promethazine HCl for the treatment of motion sickness

Purpose: To prepare and characterize orally disintegrating films (ODFs) of promethazine hydrochloride (HCl) for prompt treatment of motion sickness.Methods: Films were prepared by solvent casting method using hydroxypropyl cellulose (HPC) as film former and glycerin as plasticizer along with a saliva stimulating and sweetening agent. Nine different film formulations were prepared and evaluated for their characteristics including thickness, disintegration time, tensile strength and drug release behavior.Results: The prepared films were transparent and slightly sticky in nature with thickness that ranged from 0.22 mm to 0.29 mm and tensile strength of 0.56 N/cm² to 2.49 N/cm². The disintegration time of film formulations ranged from 26.3 to 52.7 s and a majority of formulations released approx. 80 % of the drug within 10 min with a non-Fickian diffusion pattern.Conclusion: The study concludes that the orally disintegrating films of promethazine HCl can be prepared using HPC as film former.Key words: Orally disintegrating films, Promethazine, Solvent casting, Motion sicknes