Statistical Design for Optimization and Determination of Tizanidine Hcl using Folin-Ciocalteu (Fc) as Chromogenic Reagent

A simple, sensitive spectrophotometric method has been developed for quantitative determination of Tizanidine Hydrochloride in bulk and pharmaceutical formulations with application of factorial design. In this method, Tizanidine Hydrochloride is made to react with Folin-Ciocalteu (FC) reagent under alkaline conditions forming a blue chromogen having absorption maximum at 663 nm. Beer’s law was obeyed in the concentration range of 4-36 μg/ml. Results of the analysis were validated as per ICH guidelines and by recovery studies. A 3-factor, 3-level statistical design (Box-Behnken) was used to derive a second-order polynomial equation to construct contour plots for prediction of response. Independent variables studied were the FC-reagent (X1), sodium carbonate (X2) and drug concentration (X3) and the levels of each factor were low, medium, and high. The dependent variable studied was absorbance (Y1). The aims of this study to determination and optimize the Tizanidine HCl using FC as Chromogenic reagent; the design demonstrated the role of the derived equation (polynomial) and two dimensional plots in predicting the values of dependent variable for optimization

Investigation on Dissolution Pattern and Mathematical Modeling of Drug Release of UDCA by Complextaion with b-Cyclodextrin-Choline Dichloride Coprecipitate

The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of Ursodeoxycholic acid (UDCA) from molecular inclusion complexes. The molecular inclusion complexes of UDCA with β-CD coprecipitated with CDC were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures and cyclodextrin inclusion complexes (UDCA-β-CD- CDC) were carried out. Molecular inclusion complexes of Ursodeoxycholic acid with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH 7.4. Inclusion complexes with 1:2M ratio showed maximum dissolution rate in comparison to other ratios. FT-IR spectroscopy and differential scanning calorimetry studies indicated no interaction between UDCA and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics followed by Higuchi release model. In conclusion, dissolution of Ursodeoxycholic acid can be enhanced by using the β-CD-CDC coprecipitate as a host st molecolec

Self-consistent variational theory for globules

A self-consistent variational theory for globules based on the uniform expansion method is presented. This method, first introduced by Edwards and Singh to estimate the size of a self-avoiding chain, is restricted to a good solvent regime, where two-body repulsion leads to chain swelling. We extend the variational method to a poor solvent regime where the balance between the two-body attractive and the three-body repulsive interactions leads to contraction of the chain to form a globule. By employing the Ginzburg criterion, we recover the correct scaling for the $\theta$-temperature. The introduction of the three-body interaction term in the variational scheme recovers the correct scaling for the two important length scales in the globule - its overall size $R$, and the thermal blob size $\xi_{T}$. Since these two length scales follow very different statistics - Gaussian on length scales $\xi_{T}$, and space filling on length scale $R$ - our approach extends the validity of the uniform expansion method to non-uniform contraction rendering it applicable to polymeric systems with attractive interactions. We present one such application by studying the Rayleigh instability of polyelectrolyte globules in poor solvents. At a critical fraction of charged monomers, $f_c$, along the chain backbone, we observe a clear indication of a first-order transition from a globular state at small $f$, to a stretched state at large $f$; in the intermediate regime the bistable equilibrium between these two states shows the existence of a pearl-necklace structure.Comment: 7 pages, 1 figur

Dissolution behaviour of aceclofenac-PVP coprecipitates

Aim: The objective of the present investigation was to study the effect of PVP on in vitro dissolution of aceclofenac from coprecipitates. Materials and Methods: Aceclofenac coprecipitates (CP) with different drug loadings were prepared and in vitro dissolution studies of pure drug, physical mixtures and coprecipitates were carried out. Results: Coprecipitates of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH, 7.4. Coprecipitates in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. Amorphous nature of the drug in coprecipitates was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in coprecipitates compared to the pure drug. FT- IR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in coprecipitates in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation and solubilizing effect of the carrier from the coprecipitates of aceclofenac. Conclusion: dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP

A survey of the treatment and management of patients with severe chronic spontaneous urticaria.

Chronic spontaneous urticaria (CSU) is characterized by the recurrent appearance of weals, angio‐oedema or both, occurring at least twice weekly for longer than 6 weeks.1 It is often managed with antihistamines, but occasionally requires other systemic agents in recalcitrant cases. A cross‐sectional survey was conducted by means of an internet‐based survey tool (Typeform; https://www.typeform.com). Participating consultants with a specialist interest in urticaria were identified through the specialist registers of the British Society of Allergy and Clinical Immunology (BSACI), the Improving Quality in Allergy Services (IQAS) Group and the British Association of Dermatologists (BAD), and invited to take part. The survey content was based on current CSU treatment guidelines from EAACI/GA2LEN/EDF/WAO1 and the British Society for Allergy and Clinical Immunology (BSACI).2 The EAACI/GA2LEN/EDF/WAO guidelines are a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA2LEN) (a European Union‐funded network of excellence), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO). To standardize responses, all participants were presented with a case of recalcitrant CSU (failed on maximum dose of nonsedating antihistamines and montelukast), requiring alternative systemic treatment. Questions covered usage of systemic treatments, routine disease severity assessments, adherence to treatment guidelines and perceived barriers to prescribing. Responses (Table 1) were received from 19 UK consultants (26 surveys sent; completion rate 73%), 15 of whom had > 10 years’ experience in the treatment of CSU. The majority were allergy (58%) and dermatology consultants (37%). Of the 19 consultants, 56% provide a dedicated urticaria service, 37% treat both adult and paediatric patients, and the majority (79%) use systemic medications other than antihistamines and montelukast. Omalizumab and ciclosporin were the most commonly used first‐line agents (47% and 27% respectively) (Fig. 1). The majority (84%) of consultants use validated measures to assess disease severity, including the weekly Urticaria Activity Score (UAS‐7, 63%), the Physician Global Assessment (63%), the Patient Global Assessment (44%) and the Dermatology Quality of Life Index (DLQI) (38%). Guidelines are used by 89% to direct their management of CSU, with 50% using the EAACI/GA2LEN/EDF/WAO guideline,1 compared with 31% primarily using the BSACI guideline.2 The main perceived barriers to prescribing systemic medications were potential adverse effects (AEs) (32% strongly agreed), potential long‐term toxicity (26% strongly agreed), cost of treatment (42% strongly agreed), and views expressed by the patient and their family (37% agreed)

Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties.

Bronchoalveolar lavage (BAL) is a simple, yet informative tool in understanding the immunopathology of various lung diseases via quantifying various inflammatory cells, cytokines and growth factors. At present, this traditional method is often blended with several robust and sophisticated molecular and biological techniques sustaining the significance and longevity of this technique. Crucially, the existence of slightly distinct approaches and variables employed at different laboratories around the globe in performing BAL aspiration indeed demands an utmost need to optimize and develop an effective, cost-effective and a reproducible technique. This mini review will be of importance to the biological translational scientist, particularly respiratory researchers in understanding the fundamentals and approaches to apply and consider with BAL aspiration techniques. This will ensure generating a meaningful and clinically relevant data which in turn accelerate the development of new and effective therapeutic moieties for major respiratory conditions

Mechanism of mesenchymal stem cells as a multitarget disease-modifying therapy for parkinson's disease.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders, affecting the basal nuclei, causing impairment of motor and cognitive functions. Loss of dopaminergic (DAergic) neurons or their degeneration and the aggregation of Lewy bodies is the hallmark of this disease. The medications used to treat PD relieve the symptoms and maintain quality of life, but currently, there is no cure. There is a need for the development of therapies that can cease or perhaps reverse neurodegeneration effectively. With the rapid advancements in cell replacement therapy techniques, medical professionals are trying to find a cure by which restoration of dopamine neurotransmitters can occur. Researchers have started focusing on cell-based therapies using mesenchymal stem cells (MSCs) due to their abundance in the body, the ability of proliferation, and immunomodulation. Here we review the MSC-based treatment in Parkinson's disease and the various mechanisms it repairs DAergic neurons in parkinsonian patients

Formulation and evaluation of controlled release ethylcellulose and polyethylene glycol microspheres containing metoprolol tartrate.

Metoprolol tartrate is rapidly absorbed from both gastric and intestinal regions, after oral administration. To retard the release rate of the metoprolol tartrate, microspheres were prepared with varying concentrations of a mixture containing ethylcellulose and polyethylene glycol-6000. The prepared microspheres were evaluated for various physicochemical characteristics and in vitro drug release. The percent yield of microspheres was in the range of 75.2-87.3%. The particle size of microspheres was found to be in the range of 73.2-85.5 μm. Fourier transform-infrared spectral analysis and differential scanning calorimetry concluded the absence of any interaction between the drug and the carriers. The release time profile of metoprolol tartrate from microspheres in 0.1 N hydrochloric acid solution was to the extent of 33.4-60.2%. The complete release of metoprolol tartrate occurred from MPT-3 and MPT-4 in phosphate buffer solution (pH 7.4) within 8 and 7 h, respectively, whereas the incomplete release (72.3%) occurred from MPT-1. Nearly, the complete release (98.5%) of metoprolol occurred from MPT-2 in 10 h. Formulation MPT-2 would be a preferred formulation. The release of metoprolol involves diffusion rate limited (R2 = 0.9865) as a mechanism from drug release. The prepared microspheres of metoprolol tartrate eliminate the need for multiple dosing and provide patient compliance

TLC Separation of Closely Related Amino Acids

761-76