EXTRACTION OF A WATER SOLUBLE BIOACTIVE HYPOXOSIDE AND ITS DEVELOPMENT INTO AN ETHOSOMAL SYSTEM FOR DEEP DERMAL DELIVERY

Objective: This study was aimed to extract Hypoxoside, a water soluble phytochemical, from the corms of Hypoxis hemerocallidea, and incorporate it into a suitable transdermal carrier system to increase its penetrability and deep dermal delivery for potential antioxidant and anticancer activity.Methods: The extraction of Hypoxis hemerocallidea corms was carried out by continuous hot extraction method. This extract (20 mg/ml) was loaded into ethosomal vesicular system by cold method and optimized by varying proportions of lecithin and ethanol. The optimized system was then subjected to characterization in terms of particle size, polydispersity index (PDI), entrapment efficiency and invitro permeation and penetration studies.Results: The optimized vesicle with size of 176.2±11 nm, PDI of 0.231 and entrapment efficiency of 74.2±2.3% was obtained which showed a sustained release pattern of the hypoxoside from the vesicular system. Confocal laser scanning microscopy (CLSM) demonstrated that the vesicles were able to efficiently traverse the skin to a depth of 117.29 µm whereas the mechanism of vesicle-skin interaction was confirmed by histopathological study.Conclusion: The study indicated that with the development of an efficient delivery system a water soluble phytochemical with antioxidant and anticancer properties can be efficiently delivered to the skin.Â

In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA), ácido fúlvico (FA), β-ciclodextrina (β-CD), 2-hidroxipropil-β-ciclodextrina (HP-β-CD) e cafeína (Caff). O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional, calorimetria de varredura diferencial (DSC), difração de raios-X (XRD), ressonância magnética nuclear (RMN) e espectroscopia de massas. Além disso, os complexos foram avaliados in vivo, em ratas, no tocante à sua eficácia no tratamento de candidíase vaginal. Entre os cinco complexos testados, o complexo de ácido fúlvico-itraconazol foi o que apresentou melhor solubilidade, bem como melhor eficácia in vivo e, portanto, pode ser explorado para o desenvolvimento de uma formulação comercial para o tratamento de candidíase vaginal

Stepping into small shoes: Gaining user perspective on appropriate administration devices for paediatric medication in India

A cross sectional pan-India study about use of administration devices for paediatric oral and inhalation medicines was conducted with a diverse pool of participants of various age groups. Via 634 respondents from more than 15 states in India, this study has identified the administration devices commonly used by parents/caregivers for children 0 to 18 years and by children over 10 years. It has provided insights on device ease of use, challenges faced and recommendations to facilitate the correct use of administration devices for paediatric oral and inhalation medicines. Ethics approval (DPSRU-BREC/2020/A/008)) was obtained from the Biomedical Research Ethics Committee of Delhi Pharmaceutical Sciences and Research University. The survey was completed by parents only (n = 514) and jointly by both parents and children (n = 120). The mean age of the child was 7.2 ± 4.96 years. 72% of the respondents reported that an oral medicine had been taken recently, 6.3% reported that an inhaled medicine had been taken and the remaining 21.9% reported that both an oral and inhaled medicine had been taken. The use of measuring cup was most prevalent followed by household spoons. The mean of the score for ease of use was found to be highest 4.6 ± 0.50 for oral syringe and lowest (3.8 ± 0.76) for measuring cups. The majority of them found the oral device easy to use. Difficulties were reported mostly for measuring cups and household spoons and were related to a lack of user instructions and measuring difficulties. The respondents who found the device easy to use had mostly received clear instructions from healthcare professionals. Compared to oral devices, there were very limited responses for inhalation devices (n = 175/634). Nebulisers with facemasks were most frequently used followed by manually actuated Metered dose inhalers with and without spacer. The mean of the ease-of-use score for dry powder inhalers was found to be highest (4.2 ± 0.37) followed by mist inhalers (4.0 ± 0) and manually actuated pressurised metered dose inhalers (4.0 ± 0.71). The nebulisers with facemask were reported to be difficult to use by most of the respondents despite receiving clear instructions from healthcare professionals.// The study findings add evidence to the understudied area of user experiences and perspectives on administration devices for oral and inhalation medicines in India. It highlights a need for initiatives to improve the usability, availability, and affordability of administration devices for children in India. Awareness on the importance of proper use of devices needs to be raised and sustained about the existence of affordable administration devices

Data of aromatase inhibitors alone and in combination with raloxifene on microarchitecture of lumbar vertebrae and strength test in femoral diaphysis of VCD treated ovotoxic mice

Currently, the third generation aromatase inhibitors are the drugs of choice for treatment of early and advanced breast cancer in postmenopausal women. The negative impact of these drugs on bone health is the significant limiting factor during this therapy. Here we report the effect of two aromatase inhibitors viz. letrozole and exemestane alone and in combination with raloxifene on lumbar vertebrae and femoral diaphysis after one month of treatment but no discernible effects were observed on bone when tested by micro CT and strength test except in trabecular number which was reduced in lumbar vertebrae following letrozole and exemestane. Further studies with letrozole and exemestane should be done at higher doses for longer duration of time to check whether effects are observed in other parameters as well. The data is an extension of our published work in Mol. Cell Endocrinology (A. Kalam, S. Talegaonkar, D. Vohora, 2017) [1] describing letrozole-induced bone loss on femoral epiphysis and its reversal by raloxifene

Developed and validated stability indicating HPLC method for the determination of epirubicin in bulk drug, marketed injection and polymeric nanoparticles

Present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for routine quality control of epirubicin (EPI) in bulk drug, marketed injections and polymeric nanoparticles. Separation was carried out by C18 column. Isocratic elution was carried out using mobile phase A: 0.16% o-phosphoric acid solution, B: acetonitrile and methanol mixture (80:20, v/v) in the ratio of 60:40 (A: B) while the flow rate was maintained at 1mL/min. Analyses were performed at 233.5 nm using PDA detector. Excellent linear relationship was observed between peak-area versus drug concentration in the range of 1.0-100.0 μg/mL (r2, 0.999). Developed method was found to be sensitive (Limits of detection and quantification were found to be ~8 ng/mL and ~25 ng/mL, respectively), precise (RSD <1.0%, for repeatability and <2.0% for intermediate precision, within acceptable ranges of precision), accurate (recovery in different dosage form, 94.65 -100.26%, within acceptable range, 80-120%), specific and robust (% RSD <2, for system suitability parameters). Stress-induced degradation studies demonstrated that method can suitability be applied in the presence of degradants. Developed method has been successfully applied for the determination of entrapment efficiency, drug loading, in vitro release profile, in vitro permeation studies as well as stability assessment of polymeric nanoparticles

Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms

Selective serotonin reuptake inhibitors (SSRIs) are currently the treatment of choice in depression and constitute major portion of prescription in depressive patients. The role of serotonin receptors in bone is emerging, raising certain questions regarding the effect of blockade of serotonin reuptake in the bone metabolism. Clinical studies have reported an association of SSRI antidepressants which with increase in fracture and decrease in bone mineral density. This review focus on recent evidence that evaluate the association of SSRIs with the risk of fracture and bone mineral density and also the probable mechanisms that might be involved in such effects

Design and development of novel bioadhesive niosomal formulation for the transcorneal delivery of anti-infective agent: In-vitro and ex-vivo investigations

Gatifloxacin eye drops are frequently used in eye infections. However such formulations have a major drawback i.e. short duration of action and usually require 4–6 times installations daily. A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing frequency. Vesicles were prepared by solvent injection method using cholesterol and Span-60. An extensive optimization of formulation was done using different ratios of cholesterol, Span-60 and drug, revealed NS60-5 (cholesterol: span-60 50: 50 and drug content of 20 mg) to be the optimized niosome formulation. NS60-5 had shown a highest entrapment efficiency of 64.9 ± 0.66% with particle size 213.2 ± 1.5 nm and zeta potential −34.7 ± 2.2 mV. Optimized niosomes were also coated with different concentrations of chitosan and evaluated. Permeation studies had revealed that optimized niosomes (86.77 ± 1.31%) had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution (37.19 ± 1.1%). Longer retention potential of the coated niosomes was further verified by fluorescence microscopy. Study revealed that simple dye solution got easily washed out with in 6 h. The uncoated niosomes (NS60-5) showed a longer retention (more than 6 h), which was further enhanced in case of coated niosomes i.e. CNS60-1 (more than 12 h). Antimicrobial studies had shown the better efficacy of CNS60-1 (zone of inhibition) when compared to marketed formulation. The final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations