Automation in pharmaceutical sector by implementation of artificial intelligence platform: a way forward

Worldwide, there are technological advances that swift automation in several aspects of the pharmaceutical industry such as pharmacovigilance, clinical research, medical affairs, and marketing. Innovative technology like artificial intelligence (AI) emphasizes the massive use of the internet for drug development, drug safety, data analytics, communication marketing, and customer engagement to achieve the goal of pharmaceuticals and patient-centric healthcare. Presently, escalating the number of individual case safety reports (ICSRs) necessitate the support of AI in the transformation of drug safety professional. AI can be transformed and evolve the clinical trial process from the conventional method alongside benefited the cutting cost, enhancing the trial quality, and alleviate trial time by almost half. Today, AI may be efficiently implemented to lower the cost of medical information requests, besides the online chatbots to communicate with health care professionals (HCPs) and consumers. There are numerous forthcoming uses of AI which need to be executed for renovation in the field of pharmaceuticals

Azimuthal asymmetries in DD-meson and jet production at the EIC

We study the azimuthal asymmetries in back-to-back leptoproduction of $D$-meson and jet to probe the gluon TMDs in an unpolarized and transversely polarized electron-proton collision at the kinematics of EIC. We give predictions for unpolarized cross-sections within the TMD factorization framework. In $D$-meson and jet formation, the only leading order contribution comes from the photon gluon fusion process. We give numerical estimates of the upper bound on the azimuthal asymmetries with the saturation of positivity bounds; also, we present the asymmetries using a Gaussian parameterization of TMDs. We obtain sizable asymmetries in the kinematics that will be accessible at EIC.Comment: 19 pages, 13 figures, the version to be published in PR

DEVELOPMENT AND VALIDATION OF STABILITY INDICATING RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF ASPIRIN, ROSUVASTATIN, CLOPIDOGREL IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: To develop a novel, accurate, precise and linear reverse phase high-performance liquid chromatography (RP-HPLC) and Stability Indicating Assay Method (SIAMs) for simultaneous, qualitative and quantitative estimation of aspirin, rosuvastatin and clopidogrel in bulk and pharmaceutical dosage form as per International Conference on Harmonization (ICH) guidelines.Method: In the present work, good chromatographic separation was achieved by isocratic method using a BISCOF HPLC C18 column (250 mm ×4.6, 5 µm) and a mobile phase consisting of water at pH 2.51 with 0.1 % (v/v) orthophosphoric acid (OPA): acetonitrile in the ratio 50:50, at a flow rate of 1 ml/min. The effluents obtained were monitored at 237 nm with the UV-visible detector.Results: The retention time of aspirin, rosuvastatin, and clopidogrel was found to be 4.3 min, 7.6 min and 16.6 min respectively. For linearity seven-point calibration curves were obtained in a concentration range from 1-7 µg/ml for aspirin, rosuvastatin and clopidogrel with correlation coefficient 0.999, 0.9989, 0.9988 respectively. The high recovery values (99%-101%) indicate a satisfactory accuracy. The low percent relative standard deviation (% RSD) values in the precision study reveal that the method is precise. In the present study stability indicating an RP-HPLC method for the combination was tested by degrading the drugs together under various stress condition like acid, base and neutral hydrolysis, oxidation, thermal and photolytic stress which is recommended by ICH.Conclusion: The developed RP-HPLC method is simple, economic, specific, accurate and precise for the simultaneous estimation of aspirin, rosuvastatin, and clopidogrel in the combined capsule dosage form. The developed stability indicating analytical method can be used to check the stability of the compounds and was found suitable to determine % degradation of drugs in pharmaceutical dosage form

DESIGN, SYNTHESIS, DOCKING STUDIES AND BIOLOGICAL EVALUATION OF 2-PHENYL-3-(SUBSTITUTED BENZO[d] THIAZOL-2-YLAMINO)-QUINAZOLINE-4(3H)-ONE DERIVATIVES AS ANTIMICROBIAL AGENTS

Objective: A new series 2-phenyl-3-(substituted benzo[d] thiazol-2-ylamino)-quinazoline-4(3H)-one was prepared by the fusion method by reacting 2-phenyl benzoxazine with 2-hydrazino benzothiazole and it was evaluated for their antimicrobial activity against gram positive, gram negative bacteria and fungi.Methods: Titled compounds were synthesized by fusion reactions. These compounds were evaluated by in vitro antibacterial and antifungal activity using the minimum inhibitory concentration and zone of inhibition methods. The synthesized compounds were characterized with the help of infrared, NMR and mass spectral studies. The benzothiazole moiety and the quinazoline ring have previously shown DNA gyrase inhibition and target related antibacterial activity. Thus, molecular docking studies of synthesized compounds were carried out (PDB: 3G75) to study the possible interaction of compounds with the target. The batch grid docking was performed to determine the probable.Results: These compounds showed significant activity against gram positive and gram negative bacteria as well against the fungi. The compound A5 was found to be active against B. subtilis, P aeruginosa and C. albican at 12.5 µg/ml MIC. The compound A3 was found to be active against all microbial strains selected at 25 and 12.5 µg/ml MIC.Conclusion: Though the relationship between the activities shown by these compounds in, the antimicrobial study is still to be established, the docking studies conducted found to be consistent with antimicrobial results. Thus the results indicate that the designed structure can be a potential lead as an antimicrobial agent

Effects of Strength Based Supportive Therapy on Family Functioning and Coping among Persons with Alcohol Dependence Syndrome

Background: Alcohol dependence is a complex behaviour with far-reaching harmful effects on the family, work, society, as well as on the physical and mental health of the individual. Epidemiological studies conducted in India showed that 20-30% of our population is using alcohol at a harmful level. Mental health professionals provide support and understanding of the illness for the affected individual and family members. They work together on planning treatment; provide mutual support and understanding of the disorder. Aim: To study the effects of strength based supportive therapy on family functioning and coping of persons with alcohol dependence syndrome. Methodology: This was a hospital based intervention study. It had adopted the quasi-experimental before and after with control group research design. Participants were randomly allocated to the experimental and control groups. 10 persons with alcohol dependence syndrome were selected for the study  five each person with alcohol dependence syndrome and their family members were assigned in the control group (treatment as usual group; TAU) and five persons with alcohol dependence syndrome and their family members were assigned in the experimental group (treatment as usual positive family intervention group). Family functioning was assessed through McMaster family assessment device Patients were assessed through brief cope. Result: The study results indicated a significant improvement in various domains of family functioning in experimental group participants compared to the treatment as usual group. It has also noted improvement in coping among patients. Conclusion: strength based supportive intervention useful for the caregivers as well as it also helps in improving coping among person with alcohol dependence syndrome. Keywords: Strength based supportive therapy, alcohol dependence, caregiver

Prolactin level in umbilical cord blood of newborn and its relation to respiratory distress syndrome

Background: Production of lower concentrations of prolactin in fetus is considered as one of the major contributor for the development of respiratory distress syndrome (RDS) in newborns considerably in pregnants with maternal complications. Hence the present study was conducted with the objective to measure the serum level of cord blood prolactin in normal pregnancy and in pregnancy with maternal complications and its association with development of RDS in newborn.Methods: In this prospective study of 100 women, 28 with normal pregnancy (Group A) and 72 with abnormal pregnancies (Group B) were included in the study. Umbilical cord blood was collected and serum prolactin level was estimated using radio-immuno assay. The obtained values were correlated with prevalence of RDS in neonates and maternal complications.Results: The average age of pregnant women participated in Group A was 26 years and Group B was 27 years. In Group A 2 babies with birth weight of 2001-3000 gm had a cord serum prolactin level of 216±137.8 ng/mL developed RDS. In Group B the level of prolactin was 285±276 and 326±132 ng/mL in 4 RDS babies with birth weight of <1000 gm and 1000-2000 gm respectively. It was observed that cord serum prolactin levels had no correlation with the mode of delivery, sex of newborn, steroid therapy. In Group A, 2 neonates developed RDS which were of gestational age between 32-35 weeks with mean prolactin level of 216 ng/ml, while in Group B, 1 neonate with gestational age less than 32 weeks and mean prolactin level of 480 and 4 neonates of 32-35 weeks with mean prolactin level of 266 ng/mL developed RDS. Out of 27 mothers with complications of PIH, 3 developed RDS. 1 case each from IUGR and twins developed RDS respectively.Conclusions: The risk of RDS is less in newborn with high prolactin level than in newborns with low prolactin levels. So prolactin might have a role in fetal lung maturation

EXPERIMENTAL STUDY TO EVALUATE THE ANTINOCICEPTIVE ACTIVITY OF FLUOXETINE AND ITS INTERACTION WITH NALOXONE AND ONDENSETRON IN MICE

Objectives: Evaluate antinociceptive activity of fluoxetine and the interaction of fluoxetine with naloxone and ondansetron. Methods: 32 albino mice of either sex were divided into 4 groups of 8 mice each: group I received normal saline, group II received fluoxetine; group III received fluoxetine + naloxone; group IV received  fluoxetine + ondansetron. Fluoxetine and naloxone were given subcutaneously whereas ondansetron was given intraperitoneally. Eddy’s hot plate analgesiometer was used. Latency of licking of paw or jumping from the hot plate was recorded at intervals  after giving study drugs in each group. Results: Fluoxetine produced a significant increase in the latency of licking of paw or jumping as compared to control at all time intervals except at 120 minutes with onset of antinociceptive effect within 30 min (p&lt;0.01) and maximum effect at 60 min time interval  (p&lt;0.001). There was no significant difference between the control group and the fluoxetine + naloxone or fluoxetine + ondansetron group at any time point. Pre-treatment with naloxone and ondansetron antagonized the antinociceptive effects of fluoxetine. Conclusion: Administration of naloxone and ondansetron in fluoxetine treated mice antagonized the antinociceptive activity of fluoxetine. Therefore, antinociceptive activity of fluoxetine may be mediated through µ-opiod and 5HT3 receptors. Keywords: anti-nociceptive, Eddy’s hot plate, fluoxetine, naloxone, ondansetron

Hepatitis B virus DNA polymerase gene polymorphism based prediction of genotypes in chronic HBV patients from Western India

Background: Hepatitis B Virus (HBV) infection is one of the major causes of liver cirrhosis, hepatocellular carcinoma and deaths due to the acute or chronic consequences worldwide. HBV is distributed into various genotypes based on nucleic acid sequence variation.Objectives: To develop a method of HBV genotyping and drug resistance interpretation using partial sequencing of polymerase gene.Methods: This study was performed on 98 HBV infected patients’ serum samples from Western India. A nested PCR protocol was designed for amplification of pol gene from HBV genome and Sanger’s sequencing of the gene fragment. Sequences were aligned with HBV reference sequences for phylogenetic analysis and for characterization of genetic diversity. Drug resistance mutations were screened using HBVSeq program from Stanford University.Results: Distribution of HBV genotypes showed predominance of genotype D, circulating in 76 (77.55%) patients (p &lt; 0.05). Genotypes A and C were less prevalent and were identified in 4 (4.08%) and 18 (18.37%) patients, respectively. Anti-retroviral drug resistance mutations were not detected in any patient.Conclusion: A method for determination of HBV genotypes using pol gene sequencing which simultaneously detects major drug resistance mutations has been established. HBV genetic diversity may play an important role in treatment decision.Keywords: Hepatitis B virus, nested PCR, genotype, sub-genotypes, YMDD mutation

Optimal sequence of hole-making operations using particle swarm optimization and modified shuffled frog leaping algorithm

Tool travel and tool switch scheduling are two major issues in hole-making operations. It is necessary to find the optimal sequence of operations to reduce the total processing cost of hole-making operations. In this work therefore, an attempt is made to use both a recently developed particle swarm optimisation algorithm and a shuffled frog leaping algorithm demonstrating in this way an example of plastic injection mould. The exact value of the minimum total processing cost is obtained by considering all possible combinations of sequences. The results obtained using particle swarm optimisation and shuffled frog leaping algorithm are compared with the minimum total processing cost results obtained by considering all possible combinations of sequences. It is observed that the results obtained using particle swarm optimisation and shuffled frog leaping algorithm are closer to the results of the minimum total processing cost obtained by considering all possible combinations of sequences presented in this work. This clearly shows that particle swarm optimisation and shuffled frog leaping algorithm can be effectively used in optimisation of large scale injection mould hole-making operations