Effect of Cyclodextrin Derivatization on Solubility and Efficacy of Drugs

Cyclodextrins (CDs) possess cyclic structure having (α-1,4)-linked glucopyranose units making them less vulnerable to enzymatic degradation as than the linear dextrins. Commonly used natural CDs are α-CD, β-CD, and ɣ-CD with truncated cone-like appearance having lipophilic central cavity and hydrophilic exterior surface. The problem of low aqueous solubility of natural CDs can be addressed by reacting them with various reagents to produce water-soluble derivatives. CD derivatives can be categorized in many ways depending upon their substituents, biological activity, polarity, and size. The derivatization of natural CDs produces noncrystalline and amorphous forms with higher water solubility that are physically and microbiologically stable for prolonged time period. Variety of methods can be used to determine average degree of substitution for a modified CD. Dissociation by dilution is considered as major release mechanism of drugs from complex. It is essential to optimize the amount of CDs for a given preparation because they can either retard or promote drug delivery through biological membrane

Design and evaluation of sodium alginate-based hydrogel dressings containing Betula utilis extract for cutaneous wound healing

Traditional wound dressings have a limited capacity to absorb exudates, are permeable to microbes, and may adhere to wounds, which leads to secondary injuries. Hydrogels are promising alternative dressings to overcome the above challenges. In this study, we developed sodium alginate-based hydrogel films loaded with Betula utilis bark extract. These films were prepared via solvent-casting crosslinking method and evaluated for wound healing activity. Prepared films were 0.05–0.083 mm thick, flexible with folding endurance ranging from 197–203 folds, which indicates good physical properties. Optimized formulations exhibited successful loading of extract in the film matrix without any interaction as confirmed by FTIR. Maximum zone of inhibition against Gram-positive and Gram-negative bacteria was achieved by optimum formulation (B6), i.e., 19 mm and 9 mm, respectively, with > 90% scavenging activity. Furthermore, this optimum formulation (B6) was able to achieve 93% wound contraction in rats. Histograms of the optimized formulation treated group also revealed complete reepithelization of wounds. Conclusively, our extract-loaded hydrogel dressing successfully demonstrated its potential for cutaneous wound healing

Cyclodextrins: An Overview of Fundamentals, Types, and Applications

Cyclodextrins are one of the most interesting pharmaceutical excipients with substantial theoretical and applied impacts in pharmaceutical industry. Even though the chemical foundation of these macrocyclic molecules was laid more than 100 years ago by Villiers and Schardinger, it was not until recently that cyclodextrins have been regarded as a subject of numerous potential pharmaceutical applications including inclusion complexation. This particular chapter discusses the fundamental concepts of cyclodextrin chemistry, structure, properties, and host-guest interaction with a special focus on molecular dynamics. Further in this regard, applications of cyclodextrins and numerous drug delivery approaches including novel lipid-based nanosystems are also highlighted

Comparison of solvent evaporation and ultrasonicassisted production methods in the development of nimesulide nanosponges and their characterization

Purpose: To compare solvent evaporation and ultrasonic assisted synthesis in preparation of nimesulide nanosponges using polyvinyl-alcohol and Eudragit L100 as a polymer/copolymer and dichloromethane as a cross linker.Methods: Twelve formulations of nimesulide were prepared, six with each method by varying the ratios of both polymer and co-polymer. The resulting nanosponges were evaluated characterized by preformulation studies, production yield (%), differential scanning calorimeter, x-ray diffraction, Fourier transformation infrared spectroscopy, scanning electron microscopy, entrapment efficiency (%), actual drug content (%) and in-vitro dissolution studies.Results: The results revealed that the formulation with high amounts of co-polymer in both methods showed crystalline structures with enhanced dissolution rates in basic media. Drug entrapment was higher for products prepared by solvent evaporation method (74 %) than that prepared by ultrasonic assisted method (61 %). This correlates with the enhanced dissolution rates for products by solvent evaporation method and increased solubility due to drug-polymer complex formation.Conclusion: Formulations made by solvent evaporation method demonstrate higher production yield and drug entrapment. However, both methods exhibit enhanced dissolution rates in basic medium generally as well as other characteristics that are comparable to nanosponges reported in the literature with regard to their comb like structure

Development, stabilization, and characterization of nanoemulsion of vitamin D3-enriched canola oil

In this study, the oil-in-water nanoemulsion (NE) was prepared and loaded with vitamin D3 in food-grade (edible) canola oil and stabilized by Tween 80 and Span 80 by using a water titration technique with droplet sizes of 20 to 200 nm. A phase diagram was established for the influence of water, oil, and S-Mix concentration. The outcomes revealed that the particle size of blank canola oil nanoemulsion (NE) ranged from 60.12 to 62.27 (d.nm) and vitamin D3 NE ranged from 93.92 to 185.5 (d.nm). Droplet size and polydispersity index (PDI) of both blank and vitamin D3-loaded NE results were less than 1, and zeta potential results for blank and vitamin D3 loaded NE ranged from −9.71 to −15.32 mV and −7.29 to −13.56 mV, respectively. Furthermore, the pH and electrical conductivity of blank NE were 6.0 to 6.2 and 20 to 100 (μs/cm), respectively, whereas vitamin D3-loaded NE results were 6.0 to 6.2 and 30 to 100 (μs/cm), respectively. The viscosity results of blank NE ranged from 0.544 to 0.789 (mPa.s), while that of vitamin D3-loaded NE ranged from 0.613 to 0.793 (mPa.s). In this study, the long-term stability (3 months) of canola oil NE containing vitamin D3 at room temperature (25 C) and high temperature (40 C) was observed

Validated RP-HPLC method for the simultaneous determination of glucosamine sulphate and curcumin in cream formulation: A novel stability-indicating study

Purpose: To develop and validate a stability-indicating reverse phase-high performance liquid chromatography (RP-HPLC) method for the simultaneous determination of glucosamine sulphate (GS) and curcumin (Cur) in drug solution and formulation.Methods: The optimized chromatographic conditions were achieved by passing various compositions of mobile phases over  different reverse phase chromatographic columns. Various validation parameters, including linearity, range, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, specificity and system suitability were performed and evaluated. Stability studies under stressed conditions were done to evaluate the effects of acid, alkali, oxidation, heat and degradation by UV light.Results: The validated method was linear over the concentration range of 0.094 to 1.5 mg/mL for GS and 0.125 to 1.5 mg/mL for Cur, with a correlation coefficient > 0.999. The Intra and inter-day precision were 1.9 % for GS and 0.5 % for Cur, while accuracy was 96 and 102 % for GS and Cur, respectively. Stability studies showed that GS was highly sensitive to acid, alkali and oxidation and less sensitive to heat and UV. Cur was stable against acid, heat and oxidation but sensitive to alkali and UV.Conclusion: The developed and validated method was precise and accurate for both GS and Cur and can potentially be utilized for their identification and quantification at industrial, research and quality control laboratories

Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolutio

Adolescent transport and unintentional injuries: a systematic analysis using the Global Burden of Disease Study 2019

Background: Globally, transport and unintentional injuries persist as leading preventable causes of mortality and morbidity for adolescents. We sought to report comprehensive trends in injury-related mortality and morbidity for adolescents aged 10–24 years during the past three decades. Methods: Using the Global Burden of Disease, Injuries, and Risk Factors 2019 Study, we analysed mortality and disability-adjusted life-years (DALYs) attributed to transport and unintentional injuries for adolescents in 204 countries. Burden is reported in absolute numbers and age-standardised rates per 100 000 population by sex, age group (10–14, 15–19, and 20–24 years), and sociodemographic index (SDI) with 95% uncertainty intervals (UIs). We report percentage changes in deaths and DALYs between 1990 and 2019. Findings: In 2019, 369 061 deaths (of which 214 337 [58%] were transport related) and 31·1 million DALYs (of which 16·2 million [52%] were transport related) among adolescents aged 10–24 years were caused by transport and unintentional injuries combined. If compared with other causes, transport and unintentional injuries combined accounted for 25% of deaths and 14% of DALYs in 2019, and showed little improvement from 1990 when such injuries accounted for 26% of adolescent deaths and 17% of adolescent DALYs. Throughout adolescence, transport and unintentional injury fatality rates increased by age group. The unintentional injury burden was higher among males than females for all injury types, except for injuries related to fire, heat, and hot substances, or to adverse effects of medical treatment. From 1990 to 2019, global mortality rates declined by 34·4% (from 17·5 to 11·5 per 100 000) for transport injuries, and by 47·7% (from 15·9 to 8·3 per 100 000) for unintentional injuries. However, in low-SDI nations the absolute number of deaths increased (by 80·5% to 42 774 for transport injuries and by 39·4% to 31 961 for unintentional injuries). In the high-SDI quintile in 2010–19, the rate per 100 000 of transport injury DALYs was reduced by 16·7%, from 838 in 2010 to 699 in 2019. This was a substantially slower pace of reduction compared with the 48·5% reduction between 1990 and 2010, from 1626 per 100 000 in 1990 to 838 per 100 000 in 2010. Between 2010 and 2019, the rate of unintentional injury DALYs per 100 000 also remained largely unchanged in high-SDI countries (555 in 2010 vs 554 in 2019; 0·2% reduction). The number and rate of adolescent deaths and DALYs owing to environmental heat and cold exposure increased for the high-SDI quintile during 2010–19. Interpretation: As other causes of mortality are addressed, inadequate progress in reducing transport and unintentional injury mortality as a proportion of adolescent deaths becomes apparent. The relative shift in the burden of injury from high-SDI countries to low and low–middle-SDI countries necessitates focused action, including global donor, government, and industry investment in injury prevention. The persisting burden of DALYs related to transport and unintentional injuries indicates a need to prioritise innovative measures for the primary prevention of adolescent injury. Funding: Bill & Melinda Gates Foundation

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019: A systematic analysis from the Global Burden of Disease Study 2019

Background: Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods: We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings: In 2019, 273·9 million (95% uncertainty interval 258·5 to 290·9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4·72% (4·46 to 5·01). 228·2 million (213·6 to 244·7; 83·29% [82·15 to 84·42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15–19 years was over 10% in seven locations in 2019. Although global age-standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: –1·21% [–1·26 to –1·16]), similar progress was not observed for chewing tobacco (0·46% [0·13 to 0·79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (−0·94% [–1·72 to –0·14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation: Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Funding: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation