Epidemiology and impact of chronic disease multimorbidity in India: a systematic review and meta-analysis.

Objectives: This is the first systematic review and meta-analysis of the prevalence of multimorbidity, its risk factors including socioeconomic factors, and the consequences of multimorbidity on health systems and broader society in India. Methods: A systematic review of both published and grey literature from five databases (Medline, Embase, EBSCO, Scopus, and ProQuest) was conducted including original studies documenting prevalence or patient outcomes associated with multimorbidity among adults in India. We excluded studies that did not explicitly mention multimorbidity. Three independent reviewers did primary screening based on titles and abstracts followed by full-text review for potential eligibility. The risk of bias was independently assessed by two reviewers following the Appraisal Tool for Cross-Sectional Studies. We presented both qualitative and quantitative (through meta-analysis) summaries of the evidence. The protocol for this study was prospectively registered with PROSPERO (CRD42021257281). Results: The review identified 5442 articles out of which 35 articles were finally included in this study. Twenty-three studies were based on the primary data while 12 used secondary data. Eleven studies were conducted in hospital/primary care setting while 24 were community-based. The pooled prevalence of multimorbidity based on (n=19) studies included for meta-analysis was 20% (95% CI: 19% to 20%). The most frequent outcomes were increased healthcare utilization, reduced health-related quality of life, physical and mental functioning. Conclusion: We identified a wide variance in the magnitude of multimorbidity across age groups and regions with most of the studies from eastern India. Nation-wide studies, studies on vulnerable populations and interventions are warranted.

Preparation, characterization, and evaluation of ketoconazole-loaded pineapple cellulose green nanofiber gel.

The present study involves the isolation of cellulose nanofibers from pineapple crown waste by a combined alkali-acid treatment method. The extracted pineapple nanofibers were characterized by Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, nuclear magnetic resonance, high-resolution transmission electron microscopy, and dynamic light scattering. The extracted pineapple nanofibers were then incorporated in Carbopol 934P containing ketoconazole to prepare a ketoconazole-loaded pineapple nanofibrous gel. The prepared gel formulation was evaluated for viscosity, spreadability, extrudibility, pH, drug content, and texture profile analysis. The anticipated gel formulation was further evaluated by in vitro drug release (98.57 ± 0.58 %), ex vivo drug permeation, cytotoxicity, and histopathological studies. The permeation of the drug through skin determined by the ex-vivo diffusion study was found to be 38.27 % with a flux rate of 4.06 ± 0.26 µg/cm2/h. Further, the cytotoxicity study of pineapple nanofiber and ketoconazole-loaded nanofiber gel displayed no cytotoxic on healthy vero cells in the concentration range from 10 to 80 µg/ml. The histopathological analysis exhibited no signs of distress and inflammation. In conclusion, ketoconazole-loaded pineapple nanofiber gel could be considered as a promising delivery system for topical applications.

Novel azole-sulfonamide conjugates as potential antimicrobial candidates: synthesis and biological assessment.

Background: Azole and sulfonamide molecular frameworks are endowed with potent antimicrobial activity. Materials & methods: A series of azole-sulfonamide conjugates were synthesized using click reaction of N-propargylated imidazole with azide of sulfonamide and its antimicrobial efficacy was evaluated. Results: The compounds 7c, 7i and 7r displayed promising antibacterial activities, better than the standards sulfonamide and norfloxacin. All molecules exhibited promising antifungal activity, more potent than fluconazole. Docking studies of the active conjugates signified the importance of hydrophobic interactions in hosting the molecules in the active site of dihydrofolate reductase. Conclusion: Azole-sulfonamide conjugates are more active than single sulfonamide moieties and 7c, 7i and 7r may prove valuable leads for further optimization as novel antimicrobial agents.

Exploring the Role of Self-Nanoemulsifying Systems in Drug Delivery: Challenges, Issues, Applications and Recent Advances.

Nanotechnology has attracted researchers around the globe owing to the small size and targeting properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems (SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility of ingredients in shell, decrease their application for the long run and these issues have been highlighted in this paper. The current review throws limelight on the biological aspects and process parameters. In addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive SNEDDS and several others.

Monoamine oxidase inhibitors: A concise review with special emphasis on structure activity relationship studies.

Monoamine oxidase enzyme is necessary for the management of brain functions. It oxidatively metabolizes monoamines and produces ammonia, aldehyde and hydrogen peroxide as by-products. Excessive production of by-products of monoamine metabolism generates free radicals which cause cellular apoptosis and several neurodegenerative disorders for example Alzheimer's disease, Parkinson's disease, depression and autism. The inhibition of MAOs is an attractive target for the treatment of neurological disorders. Clinically approved MAO inhibitors for example selegiline, rasagiline, clorgyline, pargyline etc. are irreversible in nature and cause some adverse effects while recently studied reversible MAO inhibitors are devoid of harmful effects of old monoamine oxidase inhibitors. In this review article we have listed various synthesized molecules containing different moieties like coumarin, chalcone, thiazole, thiourea, caffeine, pyrazole, chromone etc. along with their activity, mode of action, structure activity relationship and molecular docking studies.

Ketoprofen-FA Co-crystal: In Vitro and In Vivo Investigation for the Solubility Enhancement of Drug by Design of Expert.

The present piece of research work is framed for improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid was prepared by simple solvent-assisted grinding method, containing drug and coformer as independent variables and solubility and % drug release were assumed to be dependent variables. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in vitro and in vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the formulation showed magnified improvement in both the properties on co-crystallization. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of the drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and the pure drug was observed as 327.33 µg/ml and 556.11 µg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in Wistar rats and albino mice when compared with standard drug.

Enhancement of ketoprofen dissolution rate by the liquisolid technique: optimization and in vitro and in vivo investigations.

The objective of the current study is to evaluate the prospective of liquisolid formulation to improve the dissolution rate of ketoprofen and thereby the bioavailability. Different batches of liquisolid were prepared using polyethylene glycol 200 as a solvent, microcrystalline cellulose, and aerosil 200 as carrier and coating material, respectively. Central composite design (32) was utilized to examine the effects of independent variables (load factor and excipient ratio) on dependent variables (solubility and % in vitro drug release). Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy techniques were employed for characterization of optimized batch (LS-10) of liquisolid formulation. The half-maximal inhibitory concentration (IC50) values for in vitro anti-inflammatory activity for liquisolid formulation exhibited a higher anti-inflammatory effect than ketoprofen and physical mixture. The statistical analysis of in vivo (anti-inflammatory and analgesic) activities data demonstrated that the test (optimized formulation) treatment group resulted in quick pharmacological response in Wistar rats and Albino mice when compared with standard (pure drug) and control treatment groups. The results obtained in the present study illustrated that the liquisolid formulation could be a propitious approach to increase the bioavailability of ketoprofen and could be used in oral therapy.

Formulation and development of tacrolimus-gellan gum nanoformulation for treatment of dry eye disease.

The present study aimed at the development and evaluation of tacrolimus gellan gum nanoparticles (TGNPs) for the effective management of dry eye disease (DED) following topical application. TGNPs were developed by ionotropic gelation between gellan gum and aluminum chloride. Developed TGNPs were nanosized (274.46 ± 8.90 nm) with high % encapsulation efficiency (74.2 ± 2.4%) and loading capacity (36.14 ± 1.7%). The nanosize and spherical morphology of TGNPs was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Fourier transform infrared spectroscopy (FTIR) revealed no interaction between drug and GG. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirms the conversion of crystalline tacrolimus to amorphous post encapsulation in the nanoparticle. TGNPs showed prolonged drug release throughout 12 h and higher pre-corneal retention compared to tacrolimus solution. HET-CAM studies, histopathological evaluation, and Draize test confirmed the safety of the formulation for ocular use. Further, the pharmacodynamic studies using experimental DED in rabbits showed that TGNPs are effective in treating symptoms of DED. In conclusion, topical delivery of TGNPs could hold potential for efficient management of DED.

Ethnological aspects of COVID-19

Abstract Within recent past, coronavirus has shaken the whole world. The world faced a new pandemic of novel coronavirus 2019 (SARS-CoV-2/ COVID-19).It has socioeconomically impacted world population a lot in terms of education, economy as well as physical and mental health. This novel coronavirus is notorious enough that put human health at a great risk. Currently, researchers all over the world aretrying hard to develop a new drug/vaccine for its treatment. In past decades, the world population has faced various viral infectious illness outbreaks. Influenza A, Ebola, Zika, SARS and MERS viruses had whacked public health and economy. Medical science technology achieved the landmark in developing coronavirus (SARS-CoV-2) vaccines that are approved currently for emergency use. Some of the recently approved vaccines are developed by Pfizer and Moderna, Johnson and Johnson, Gam-COVID-vac (Sputnik V), Bharat Biotech (covaxin) andOxford-AstraZeneca vaccines (covishield) (Badenet al., 2021). Here, a short review is drafted focusingon infection, immune system, pathogenesis, phylogenesis, mode of transmission and impact of coronavirus on health and economy and recent developments in treating COVID-19

Formulation development, optimization, and in vitro assessment of thermoresponsive ophthalmic pluronic F127-chitosan in situ tacrolimus gel.

To overcome problems associated with topical delivery of tacrolimus (TCS), a thermoresponsive in situ gel system containing pluronic F127 (PL), and chitosan (CS) was developed, to enhance the precorneal retention, and to sustain the release of the drug. The PL-CS in situ gel was optimized using a 2-factor-3-level central composite experimental design by selecting the concentration of PL and CS as independent variables while gelation time, gelation temperature, and spreadability as dependent variables. The optimized formulation was developed using 22.5 g PL and 0.3 g CS, gels at 33.6 °C, in 22.93 s, and showed the spreadability of 6.2 cm. In vitro studies conducted for the optimized gel revealed the sustained release of TCS (81.73% in 4 h) and improved corneal permeation (74.13% in 4 h), compared with TCS solution. The mechanism of release of TCS followed the Higuchi model with Fickian diffusion transport. Further, histopathology and HET-CAM studies revealed that the developed gel was non-irritating and safe for ocular administration.

Development of novel anti-infective and antioxidant azole hybrids using a wet and dry approach.

Background: Considering emerging drug resistance in microbes, this work is focused on the synthesis of azole hybrids as novel antimicrobials. Materials & methods: The triazole derivatives were prepared using azide alkyne cycloaddition reaction. The antimicrobial potential of these compounds was evaluated by serial dilution method. Results: A series of azole hybrids containing benzimidazole-1,2,3-triazole skeleton was designed and synthesized via click reaction. Compound 4s showed notable antimicrobial activity against Staphylococcus aureus and Candida albicans (MIC 0.0165 µmol/ml), and 4q gives remarkable radical scavenging activity (IC50 0.0092 µmol/ml). The compounds 4a, 4k, 4o, 4s, 4x. 4m, 4n, 4s, 4t and 4x are commendable antibacterial and antifungal molecules, even better than established drugs. Molecular docking reveals that compound 4s binds with tyrosyl-tRNA synthetase residues through two H-bonds. Conclusion: Compounds 4s and 4k may be considered valuable lead compounds for further optimization as antimicrobial drugs.

Formulation and optimization of quinoa starch nanoparticles: Quality by design approach for solubility enhancement of piroxicam.

In the present study piroxicam loaded starch nanoparticles were prepared to enhance the solubility of piroxicam by nanoprecipitation technique. The preparation of nanoparticles was carried out as per central composite experimental design protocol, having concentration of starch and drug as independent variables and particle size and polydispersity index (PdI) as dependent variables. The particle size and PdI of piroxicam loaded starch nanoparticles was found to be between 282-870 nm and 0.339-0.772, respectively. After the characterization by FT-IR, TGA, XRD and SEM studies, the optimized batch was evaluated for in-vitro release study, anti-inflammatory activity and anti-oxidant activity. The in-vitro anti-inflammatory activity of piroxicam loaded starch nanoparticles was found to be more than the pure drug piroxicam whereas the anti-oxidant activity of starch is found greater than starch nanoparticles. In-vitro release study showed 98.8% release in 2 h dissolution study following supercase II transport mechanism of drug release.

Thiol functionalization of flaxseed mucilage: Preparation, characterization and evaluation as mucoadhesive polymer.

The aim of present study is to browse mucoadhesive potential of flaxseed mucilage after thiol functionalization. Thiol-derivatization of flaxseed mucilage (FSM) polysaccharide was obtained by esterification with thioglycolic acid. Thiolation of FSM was confirmed by -SH stretch in FTIR spectra at 2549.01 cm-1. Thiolated flaxseed mucilage (TFSM) was distinguished by XRD, DSC, NMR & SEM analysis. TFSM was found to contain 325.6 mM of thiol groups/g as determined by Ellman's method. The mucoadhesive property of drug loaded TFSM pellets, carried out by using chicken buccal pouch membrane, displayed greater ex-vivo bioadhesion time as compared to FSM. This improvement in mucoadhesion property of TFSM over FSM can be attributed to the formation of disulphide bond between mucus and thiolated mucilage. Further, the in-vitro dissolution study conducted in phosphate buffer (pH 6.8) provided release of diclofenac sodium for a prolonged period of 12 h for TFSM pellets by anomalous transport mechanism of drug release following zero order model of release kinetics.

Formulation and evaluation of curcumin microsponges for oral and topical drug delivery.

The aim of the present study was to improve the release rate of curcumin by microsponges prepared through quasi-emulsion solvent diffusion technique using ethylcellulose and PVA as carriers. The microsponges were characterized by FTIR, DSC, XRD and SEM studies followed by determination of total drug content and entrapment efficiency. The prepared microsponges were further filled in hard gelatin capsule shell and then loaded in carbopol gel to evaluate its potential in oral and topical drug delivery. Further, it was observed from the studies on release rate that microsponges filled in hard gelatin capsule shells (batch MS4) showed 93.2% release of curcumin whereas pure curcumin filled in capsule showed only 11.7% release in 8 h study. Furthermore, the microsponges loaded in carbopol gel were evaluated for ex vivo drug deposition studies and it was found that 77.5% of the curcumin was released within 24 h. The estimated drug remained in the skin was 207.61 ± 5.03 µg/cm2 as determined by a Franz diffusion cell. The drug release profile data were found to be fitted best into the zero-order model with anomalous transport mechanism of drug release in both cases.

Thiol derivatization of Xanthan gum and its evaluation as a mucoadhesive polymer.

Thiol-derivatization of xanthan gum polysaccharide was carried out by esterification with mercaptopropionic acid and thioglycolic acid. Thiol-derivatization was confirmed by Fourier-transformed infra-red spectroscopy. Xanthan-mercaptopropionic acid conjugate and xanthan-thioglycolic acid conjugate were found to possess 432.68mM and 465.02mM of thiol groups as determined by Ellman's method respectively. Comparative evaluation of mucoadhesive property of metronidazole loaded buccal pellets of xanthan and thiolated xanthan gum using chicken buccal pouch membrane revealed higher ex vivo bioadhesion time of thiolated xanthan gum as compared to xanthan gum. Improved mucoadhesive property of thiolated xanthan gum over the xanthan gum can be attributed to the formation of disulfide bond between mucus and thiolated xanthan gum. In vitro release study conducted using phosphate buffer (pH 6.8) revealed a sustained release profile of metronidazole from thiolated xanthan pellets as compared to xanthan pellets. In conclusion, thiolation of xanthan improves its mucoadhesive property and sustained the release of metronidazole over a prolonged period.

Psyllium arabinoxylan: carboxymethylation, characterization and evaluation for nanoparticulate drug delivery.

The objective of present investigation was to optimize the interaction between carboxymethylated psyllium arabinoxylan and chitosan to prepare polyelectrolyte naoparticles for drug delivery applications. Arabinoxylan extracted from psyllium was carboxymethylated by reacting with monochloroacetic acid under alkaline conditions. Carboxymethylation of psyllium arabinoxylan was observed to increase its crystallinity, improve thermal stability and decrease the viscosity. Further, the effect of concentrations of carboxymethylated arabinoxylan and chitosan on the particle size and particle size distribution of ibuprofen loaded polyelectrolyte nanoparticles was screened using two-factor, three-level central composite experimental design. The results of optimization study revealed that the formation of nanometric polyelectrolyte is favored at the median level of carboxymethylated arabinoxylan and chitosan concentration. The optimal concentrations of carboxymethylated arabinoxylan and chitosan were found to be 0.0779% (w/v) and 0.0693% (w/v) respectively, which provided polyelectrolyte particles of size 337.2 nm and polydispersity index 0.335. Further, polyelectrolyte complex nanoparticles were found to release ibuprofen over a prolonged period of 10h following Higuchi's square root release kinetics with the mechanism of release being combination of diffusion and erosion of matrix.

Thiol modification of psyllium husk mucilage and evaluation of its mucoadhesive applications.

Thiol functionalization of psyllium was carried out to enhance its mucoadhesive potential. Thiolation of psyllium was achieved by esterification with thioglycolic acid. Thiolation was observed to change the surface morphology of psyllium from fibrous to granular and result in a slight increase in the crystallinity and swelling. Thiolated psyllium was found to contain 3.282 m moles of thiol groups/g of the polymer. Mucoadhesive applications of thiolated psylium were explored by formulating gels using metronidazole as the model drug. On comparative evaluation thiolated psyllium gels showed 3-fold higher mucoadhesive strength than the psyllium gels as determined by modified physical balance using chicken buccal pouch. The results of in vitro release study revealed that thiolated psyllium gels provided a prolonged release of metronidazole. Further, the psyllium and thiolated psyllium gels were found to release the drug following first-order kinetics by combination of polymer relaxation and diffusion through the matrix.

Functionalization of chitosan/methylcellulose interpenetrating polymer network microspheres for gastroretentive application using central composite design.

This study focuses on evaluation of the chitosan methylcellulose interpenetrating polymer network (CS/MC IPN) microspheres intended for mucoadhesive gastroretentive application and the optimization of formulation of cinnarizine-loaded CS/MC IPNs using response surface methodology (RSM). A central composite design (CCD) for two factors at three levels each was employed to systematically evaluate the effect of critical formulation variables, namely ratio of polymers (X1) and glutaraldehyde (X2) on geometric mean diameter (dg), swelling index (SI), percent encapsulation efficiency (EE), percent mucoadhesion at the end of 4 h (MA), and time taken for 50% of drug release (T(50)). Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, SI, EE, MA, and T(50) for the optimized formulation were found to be 61.32 ± 1.38 µm, 2.38 ± 0.06, 84.13 ± 1.32%, 73.85 ± 2.78%, and 432.21 ± 26.15 min, respectively, which were in close agreement with those predicted by the mathematical models. The drug release was extended up to 16 h and release rates were fitted to the Power law equation and Higuchi's model to compute the diffusional parameters. The high degree of prognosis (due to low values of error) obtained using RSM corroborates that a two-factor CCD is quite efficient in optimizing drug delivery systems that exhibit nonlinearity in response(s). The results thus indicate that CS/MC IPNs could be employed in the future as potential gastroretentive systems for weakly basic drugs. LAY ABSTRACT: The present research explores the ability of a network of two biopolymers-chitosan (CS) and methylcellulose (MC)-to prolong the stay of a dosage form in the stomach, in the form of mucoadhesive microspheres, and to sustain the release of cinnarizine from the same. The controlled release formulation was designed using an optimization technique in the form of response surface methodology (RSM) employing a central composite design (CCD). Further, the various batches of formulation were evaluated for their degree of mucoadhesiveness, which is related to the concentration of the polymers used and also on the amount of crosslinking agent required to form the interpenetrating network (IPN) between the two polymers. For the finally optimized formulation, the experimental value of percent mucoadhesion after 4 h was found to be 77.23 ± 2.78% and the time taken to release 50% of drug was 5.60 ± 0.32 h. The values were in close agreement with those predicted by the mathematical models. The low values of error obtained using RSM corroborates that a CCD is quite efficient in optimizing drug delivery systems. The results thus indicate that CS/MC IPNs could be employed in the future as potential gastroretentive systems for weakly basic drugs.