Taguchi and Quadratic via Chromogenic Design Methodology: A Better to Best Estimation Process (Tizanidine Hcl) Bulk/Pharmaceutical

A finest quantitative responsive with reproducible best method was developed using designed array (Taguchi) and Quadratic design methodology (RSM) chromomeric spectrophotometric estimation of bulk as well as pharmaceutical (Tizanidine HCl). Initially (Taguchi), orthogonal array design was applied to find significant variables as well as optimum (better) levels. By response surface (central composite; quadratic) methodology were used to ascertain optimum to optimized “Better to Best” and studied values of variables (independent significant; X1=PDAB=chromogenic reagent; FeCl3=X2=ferric ion at optimum levels with drug constant=X3) responses (dependent Y1=absorbance) models at positive and negative (+1/-1 optimum spaces) levels. More-more, designed independent factorial levels “better to best” surface models (3D) and its polynomial (2nd order) equation was predicted the finest level which further can be considered as best chromomeric estimation method. The models analysis of experimental variables and their level showed and followed good Beer’s (5-50 μg/ml) correlation at optimized significant independent best (finest) level variables and in-addition validated using pharmaceutical guidelines (ICH; international conference on harmonization) for human use

Comparative Investigation on in vitro release of extemporaneously prepared norfloxacin semisolid formulations with marketed silver sulfadiazine 1% cream, USP using model independent approach

Objective In an attempt for better treatment of bacterial infections, various semisolid formulations containing 5% w/w of norfloxacin were prepared and evaluated for in vitro drug release and in vitro skin permeability using dialysis membrane and rat abdominal skin respectively. The in vitro diffusion and permeation profile of the prepared formulation was compared with marketed silver sulfadiazine cream 1%, USP using model independent approach. Methods Various semisolid formulations were prepared with different dermatological bases using standard procedures. In vitro diffusion and permeation studies were carried out using Keshary-Chein (KC) type diffusion cell using dialysis membrane and rat abdominal skin respectively. Results The f1 lower than 15 and f2 higher than 50 indicated similarities in the in vitro diffusion and permeation profiles of the extemporaneously prepared selected semisolid formulations and marketed silver sulfadiazine 1% cream, USP. Conclusion Amongst all the semisolid formulations prepared, carbopol gel base was found to be most suitable dermatological base for norfloxacin, the results obtained for in vitro diffusion, and in vitro skin permeation studies are comparable with that of marketed silver sulphadiazine 1% cream, USP

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

Dozirani pripravci aceklofenaka za topičku primjenu: In vitro i in vivo karakterizacija

Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1 % m/m aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations.Aceklofenak je lijek nove generacije nesteroidnih protuupalnih lijekova sa izraženim protuupalnim i analgetskim djelovanjem. Dostupan je u obliku tableta od 100 mg. U ovom radu razvijeni su dozirani pripravci za topičku primjenu u svrhu smanjenja ili uklanjanja nuspojava povezanih s oralnom primjenom nesteroidnih protuupalnih lijekova. Ti pripravci mogu se upotrijebiti kao dodatak peroralnoj terapiji artritisa i srodnih bolesti. Opisana je priprava mazila, krema i gela s 1 % m/m aceklofenaka te njihova fizička svojstva, pH, mazivost, istiskivost, jednolikost sadržaja ljekovite tvari, difuzija i permeabilnost in vitro. Nakon analize rezultata za daljnja ispitivanja odabrani su gelovi pripravljeni na bazi Carbopola 940 (AF2, AF3) i makrogola (AF7). Ispitana je akutna iritacija kože, protuupalno i analgetsko djelovanje koristeći karagenom induciranu termičku hiperalgeziju i edem šape. Pripravak AF2 bio je značajno (p < 0,05) učinkovitiji u inhibiciji hiperalgezije s upalom nego pripravci AF3 i AF7. Stoga se AF2 može predložiti kao alternativa peroralnim pripravcima

Preparation, Characterization and In Vitro Evaluation of Aceclofenac Solid Dispersions

The objective of the present investigation was to study the effect of various water soluble carriers like urea, mannitol, PVP and PVP/VA-64 on in vitro dissolution of aceclofenac from solid dispersions. Aceclofenac binary solid dispersions (SD) with different drug loadings were prepared using the melting or fusion method. In vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. Solid dispersion of aceclofenac with all four carriers (urea, mannitol, PVP and PVP/VA-64) 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. Solid dispersions containing PVP showed maximum dissolution rate in comparison to formulation containing urea, mannitol and PVP/VA-64. Amorphous nature of the drug in solid dispersion was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in solid dispersion compared to the pure drug. FT-IR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and carriers in solid dispersions 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 solid dispersions of aceclofenac. In conclusion, dissolution of aceclofenac can be enhanced by the use of various hydrophilic carriers like urea, mannitol, PVP and PVP/VA-64

Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis

Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES

Circadian rhythm disruption and Alzheimer’s disease: The dynamics of a vicious cycle

All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated