For systemic drug delivery, the buccal region offers an attractive route of drug administration. Salbutamol sulfate is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It's oral bioavailability is ∼40% due to extensive first pass metabolism. Salbutamol sulfate patches were prepared using Eudragit L-100, HPMC, PVA and Carbopol 934 in various proportions and combinations using PEG-400/PG as plasticizers. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches were ranged between 0.23 ± 0.008 and 0.59 ± 0.007 mm and mass varied between 65.23 ± 3.3 and 117.92 ± 4.2 mg. Patches showed an increase in mass and swelling index with PEG-400 when compared with PG. The surface-pH of patches ranged between 6 and 7. Formulations E7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PEG-400), E12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PEG-400), F7 (7.5 mL Eudragit L-100, 15 mL HPMC K4M, 7.5 mL PVA and 2 mL PG), and F12 (7.5 mL Eudragit L-100, 7.5 mL PVA, 15 mL Carbopol and 2 mL PG) showed high folding endurance. Residence time of the tested patches ranged between 101 and 110 min. The maximum in vitro release was found to be 99.93% over a period of 120 min for formulation F12. Data of in vitro release from patches were fitted to different kinetic models such as Higuchi and Korsmeyer-Peppas models to explain the release profile. Formulations E7 and F7 were best fitted to the non-Fickian, where as formulations E12 and F12 showed Fickian/anomalous drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period.

Drugs that inhibit cyclooxygenase-2 (COX-2) while sparing cyclooxygenase-1 (COX-1) represent a new attractive therapeutic development and offer new perspective for further use of COX-2 inhibitors. Intention of this work is to develop safer, selective COX-2 inhibitors that do not produce harmful effects. A series of 55 tyrosine derivatives were designed for evaluation as selective COX-2 inhibitors and investigated by in silico for their anti-inflammatory activities using C-Docker. The results of docking study showed that 35 molecules were found to selectively inhibit the enzyme COX-2. These molecules formed stable π hydrophobic and additional van der Waals interactions in the active site side pocket of COX-2. The molecules selected from docking studies were examined through ADMET descriptors and Osiris property explorer to find its safety profile as well. The tyrosine derivatives containing toxic fragments were eliminated. The results conclude that out of 55, 19 molecules possessed best binding energy (< −3.333 kcal/mol) and these molecules had more selective and safer COX-2 inhibitor profile compared to the standard celecoxib. Graphical abstract 3-D structural interactions of COX-2 inhibiting tyrosine derivatives.

Fluoroquinolones (FQs) belong to the class of quinolone drugs that are used to treat Urinary tract infections (UTIs) through inhibition of E. coli DNA gyrase. Resistance to FQs poses a serious problem in the treatment against resistant strains of E. coli which are associated with Ser83 to Leu and Asp87 to Asn mutations at the quinolone resistance determining region (QRDR) of the GyrA subunit of DNA gyrase. Mutant DNA GyrA (mtDNA GyrA) is deemed to be a significant target for the development of novel FQ drugs. Due to resistance to FQ drugs, discovery or development of novel FQs is crucial to inhibit the mtDNA GyrA. Hence, the present study attempts to design and develop novel FQs that are efficient against resistant E. coli strains. A three-dimensional structure of the mtDNA GyrA protein was developed by homology modeling, following which 204 novel FQ analogs were designed using target based SAR. The designed ligands were then screened using molecular docking studies, through which the pattern of interaction between the ligands and the target protein was studied. As expected, the results of the docking study revealed that the molecules FQ-147, FQ-151 and FQ-37 formed hydrogen bonding and Van der Waals interactions with Leu83 and Asn87 (mutated residues), respectively. Further, the wild-type (WT), mtDNA GyrA and docking complex were studied by molecular dynamics (MD) simulations. Subsequently, all the screened compounds were subjected to a structure and ligand based pharmacophore study followed by ADMET and toxicity (TOPKAT) prediction. Finally, eighteen hit FQ analogs which showed good results for the following properties, viz., best binding score, estimated activity (MIC value) and calculated drug-like properties, and least toxicity, were shortlisted and identified as potential leads to treat UTI caused by FQ resistant E. coli. Apart from development of novel drug candidates for inhibition of mtDNA GyrA, the present study also contributes towards a superior comprehension of the interaction pattern of ligands in the target protein. To a more extensive degree, the present work will be useful for the rational design of novel and potent drugs for UTIs.

Development and characterization of mucoadhesive patches of salbutamol sulfate for unidirectional buccal drug delivery: Buccal patches of salbutamol sulfate were prepared using five different water soluble polymers in various proportions and combinations using PEG-400/PG as plasticizers. A 3² full factorial design was used to design the experiments for each polymer combination. Patches were laminated on one side with a water impermeable backing layer for unidirectional drug release. The thickness of medicated patches ranged between 0.2 and 0.4 mm and showed an increase in mass whenever PEG-400 was used as plasticizer. The surface pH of all patches approached neutral. Eight formulations which had shown high folding endurance (> 300) were selected for evaluation. Patches prepared with PEG-400 showed a high swelling index. The residence time of the tested patches ranged between 105 and 130 min. Formulations A10, A32, B10 and B32 fitted the Higuchi model best, whereas formulations A19 and B19 showed super case II transport drug release. Stability studies indicated that there was no change in the chemical and physical characteristics during the test period of 6 months.