Impact of Social Restrictions During COVID-19 on the Aquatic Levels of Antimicrobials and Other Drugs in Delhi.

The relative contribution of factors responsible for the environmental exposure of active pharmaceutical ingredients (APIs) is of interest for appropriate remedial measures. This study was carried out to evaluate the post-lockdown levels of APIs in water resources, in comparison to our previously published study from 2016. The environmental levels of 28 drugs from different classes were analyzed in surface water (Yamuna River), aquifers, and leachate samples collected from 26 locations in Delhi-NCR using the previously validated liquid chromatography-mass spectrometry (LC-MS/MS) methods. In addition, the prevalence of antimicrobial resistance in coliforms isolated from targeted surface water samples was also studied. This study revealed that more than 90% of APIs, including antibiotics, decreased drastically in both surface water and aquifers compared to our previous data. Selected samples subjected to antimicrobial resistance (AMR) analysis revealed the presence of cephalosporin-resistant coliform bacteria. Tracing cephalosporins in the surface and drain water samples revealed the presence of ceftriaxone in the drain and water samples from Yamuna River. Higher levels of ceftriaxone in landfill leachate were also found, which were found to be associated with coliform resistance and indicate the un-segregated disposal of medical waste into landfills. Social restrictions enforced due to COVID-19 resulted in a drastic decrease in antimicrobials and other APIs in aquatic water resources. Increased ceftriaxone and cephalosporin resistance was seen in coliform from surface water and drain, indicating the possibility of hospital waste and treatment-related drugs entering Yamuna River. Enforcement of the regulations for the safe disposal of antibiotics at hospitals and preliminary disinfection of hospital sewage before its inflow into common drains might help minimize the spread of antibiotic resistance in the environment.

Tear Tacrolimus Levels and Clinical Response After Adjunct Therapy With Cutaneous Application of Tacrolimus 0.1% Over Upper Eyelid Skin in Chronic Vernal Keratoconjunctivitis.

PURPOSE: The aim of this study was to evaluate the role of cutaneous application of 0.1% tacrolimus eye ointment over the skin of the upper eyelid in chronic vernal keratoconjunctivitis (VKC). METHODS: A prospective, longitudinal, noncomparative, open-label clinical study of moderate-to-severe grade steroid-dependent VKC was performed. Study participants were initiated on adjunct therapy of cutaneous application of 0.1% tacrolimus ointment twice daily on the upper eyelid skin. Ocular surface evaluation parameters, meibomian gland imaging, intraocular pressure, visual acuity, and clinical disease severity scoring were performed to assess clinical response at baseline and month 3 of therapy. Tear levels of tacrolimus were measured at month 3 using high-performance liquid chromatography tandem mass spectrometry and correlated with the clinical score. RESULTS: Palpebral form of VKC was observed in 85% of the cases, with positive family history in 5%, atopy in 7.5%, and keratoconus in 11.25%. Clinical assessment revealed improvement in 97.5% patients with discontinuation of concomitant topical steroids in 64% of patients. There were no changes in visual acuity, intraocular pressure, or ocular surface evaluation after therapy. Tacrolimus was detected in the tears of all our study patients after cutaneous application over the upper eyelid skin, proving its bioavailability with mean tear tacrolimus levels of 6.55 ± 21.43 ng/mL. Correlation analysis revealed a moderate negative correlation between the clinical score and tacrolimus concentration (Spearman correlation coefficient: -0.34, P = 0.002). CONCLUSIONS: Cutaneous tacrolimus 0.1% ointment over the upper eyelid skin is an efficacious alternative method of application in treatment of VKC, with no resultant ocular irritation.

Finger printing of counterfeit bevacizumab and identifying it before clinical use.

BACKGROUND: Bevacizumab is widely used for ophthalmic purposes. Recently, counterfeit bevacizumab has become a matter of concern. We analysed samples of suspected counterfeit formulations of bevacizumab and assessed the possibility of using simple tests in the clinic by ophthalmologists to prevent the use of counterfeit preparations in patients. METHODS: We did a protein analysis using Bradford assay and SDS-PAGE to confirm the presence of bevacizumab in 16 samples - 6 suspected and 10 others. The samples were also subjected to physicochemical analysis such as osmolarity, chloride content and pH. The samples tested negative for protein were analysed by mass spectrometry to detect drugs used in place of bevacizumab. We standardized the method of frothing and precipitation analysis for identifying authentic samples of bevacizumab before their clinical use. RESULTS: Five of the 16 samples tested were negative for the presence of bevacizumab. The physicochemical parameters also supported the protein analysis test. However, no ionizable organic compound (other drug[s]) was detected by mass spectrometry. CONCLUSION: Ophthalmic use of counterfeit bevacizumab can be prevented by simple methods such as the frothing and precipitation tests. These can identify the absence of an active drug.

Development and characterization of nanoemulsion as carrier for the enhancement of bioavailability of artemether.

The present study aimed to develop a kinetically stable nanoemulsion of artemether with improved solubility, stability and oral bioavailability. Nanoemulsion was prepared by ultrasonication technique using internal oil phase (consisted of the drug dissolved in coconut oil and span 80) and external phase (comprising tween 80 and ethanol dissolved in water). The formulations were optimized using various parameters like percentage transmittance, refractive index, drug content, viscosity, zeta potential and release rate. Stability studies were conducted for a period of 90 days using stability chambers. In vivo studies of the developed formulations were conducted on Wistar rats and data were analyzed statistically. The nanoemulsion as observed under transmission electron microscope were found to be spherical in shape with an average size of 79.0 nm and a zeta potential of -15 mV which indicated of good electrokinetic stability of nanoemulsion . Nanoemulsion was found to be clear and transparent in appearance with a percentage transmittance of 98.2. Refractive index of 1.32 of the nanoemulsion indicated the isotropic nature of the drug. Release rate of the drug from the nanoemulsion formulation was found to be quite significant (P < 0.001) as compared to the plain drug. In vivo oral bioavailability of the nanoemulsion formulation was found to be 2.6-fold higher than the plain drug (˜ 40%) as observed from pharmacokinetic studies. Thus it was observed that nanoemulsion proved itself as a promising alternate for improving the bioavailability of artemether.