JOURNAL OF DRUG DELIVERY AND THERAPEUTICS

1-7

Authors: Asheesh Singh, Parul Singh, Chandra Kant Patel

Topiramate is a new antiepileptic drug (AED) that has been approved worldwide (in more than 80 countries) for the treatment of various kinds of epilepsy. It is currently being evaluated for its effect in various neurological and psychiatric disorders. Topiramate is used alone or with other medications to prevent and control seizures (epilepsy). This medication is also used to prevent migraine headaches and decrease how often you get them. The present review includes all available information like pharmacokinetics, pharmacological action and side effects. Moreover sometimes it is necessary to monitor the therapeutic concentration of Topiramate. The pharmacokinetics of topiramate are characterised by linear pharmacokinetics over the dose range 100-800 mg, low oral clearance (22-36 mL/min), which, in immunotherapy, is predominantly through renal excretion (renal clearance 10-20 mL/min), and a long half-life (19-25 hours), which is reduced when co administered with inducing AEDs such as phenytoin, phenobarbital and carbamazepine. This paper provides a critical review of the pharmacokinetic interactions of topiramate with old and new AEDs, an oral contraceptive, and the CNS-active drugs lithium, haloperidol, amitriptyline, risperidone, sumatriptan, propranolol and dihydroergotamine. The results of many of these drug interaction studies with topiramate have not been published before, and are presented and discussed for the first time in this article.

11-18

Authors: Mohammad Zishan, Saidurrahman Saidurrahman, Anayatullah Anayatullah, Azeemuddin Azeemuddin, Zeeshan Ahmad, Md Wasim Hussain

In the present time Natural products are considered to be symbols of protection in comparison to the synthetic product that are regarded as unsafe to human life and environment. Although a large number of synthetic drugs are being added to the world of present pharmacopoeia, but still no system of medicine in the world has been able to solve all the health problems, which include diseases like Cancer. Plant-derived compounds have played an important role in the development of several clinically useful anti-cancer agents. These include vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan, etoposide, derived from epipodophyllotoxin, and paclitaxel (taxol). Several promising new agents are in clinical development based on selective activity against cancer-related molecular targets, including flavopiridol and combretastin A4 phosphate, and some agents which failed in earlier clinical studies are stimulating renewed interest. Therefore the search for innovative therapeutic constituents from plants is genuine and urgent. In India, there is an ocean of knowledge about medicinal plants and rich medicinal flora, but still only a few pearls have been searched as therapeutic agents.

28-35

Authors: Neha Jawale, Chinmay Bhangale, Mayur Chaudhari, T A Deshmukh

Transdermal drug delivery system (TDDS) is the topically administered medication, which when applied to the skin, delivers the drug through the skin for systemic effect at a predetermined and controlled rate. For the drugs, having the short biological half-life, transdermal drug delivery system is convenient. It overcomes the problems like the hepatic first pass effect, improves the compliance of patients, decreases the administration frequency, and reduce the gastrointestinal side effects, peak and valley levels in the blood are avoided. Due to having an advantage of being non-invasive, this delivery has to fulfill some parameters such as high potency, better permeability through skin and non-irritation for better compliance. Skin serves as a site of drug application for local effect as well as systemic effect. There are wide varieties of drugs for which topical or transdermal is a viable option, skin penetration enhancement techniques have been developed for such drugs. There are a number of physical methods to increase drug delivery via the skin, many of which require the use of devices and some of which hold the promise to significantly expand the spectrum of drugs that can be administered transdermally to include water-soluble molecules and macromolecules. Iontophoresis and electroporation represent electrically assisted, physical approaches to enhance delivery of drugs/macromolecules across the stratum corneum. This review highlights the detailed role of physical penetration and describes their mechanism of action.

44-49

Authors: Mohammad Amir, Vaseem Ahamad Ansari, Anup Kumar Sirbaiya, Mohammad Zishan

Amikacinis a semisynthetic derivative of Kanamycin; it was approved for clinical use in the U.S. in 1976. Amikacin is broad-spectrum and potent aminoglycoside with limited clinical use owing high dose requirement.Many gram-negative bacteria, including many strains of Pseudomonas, Enterobacter, and serratiaare inhibited by 1-20 mcg/ml amikacin in vitro. After injection of 500mg of amikacin every 12hours (15mg/kg/d) intramuscularly, peak levels in serum are 10-30 mcg/ml. Amikacinis valuable because it was more active to aminoglycoside inactivating bacterial enzymes than is gentamicin. Since it was more inflated, amikacin was reserved for treatment of infections with gentamicin-resistant organisms. Peak plasma concentration should be kept between 20-30 mg/ml and trough concentration below 10mg/ml.There is no oral form of Amikacinis available as it is not absorbed orally. Various research on oral formulation of amikacinare going onsuch assignificantly improved oral uptake of amikacin in fvb mice in the presence of crl-1605 copolymer, liposomal amikacin dry powder inhaler effect of fines on in vitro performance, thiolated chitosan nanoparticles as an oral delivery system for amikacin.

55-65

Authors: Sheo Datta Maurya, Rajeshwar KK Arya, G Rajpal, Ram C Dhakar

Nearly 40% of new drug candidates exhibit low solubility in water, which is a challenge in development of optimum oral solid dosage form in terms of formulation design and bioavailability of new pharmaceutical products. Many strategies have been used to overcome these problems either by means of modifying the solubility or maintaining the drug in dissolved form throughout gastric transit time. Much attention has focused on lipid solutions, emulsions and emulsion pre-concentrates, which can be prepared as physically stable formulations suitable for encapsulation of such poorly soluble drugs. Recently, self-micro emulsifying drug delivery systems (SMEDDS) especially have attracted increasing interest primarily because these are physically stable, easy to manufacture, can be filled in soft gelatin capsules and then will generate a drug containing micro-emulsion with a large surface area upon dispersion in the gastrointestinal tract. The emulsions will further facilitate the absorption of the drug due via intestinal lymphatic pathway and by partitioning of drug into the aqueous phase of intestinal fluids. In the present review, an overview of SMEDDS as a key technology for formulating lipophilic drugs and various factors that potentially affect the oral bioavailability of such drugs are presented.

70-72

Authors: Xialin Chen, Wenzhe Huang, Wei Xiao

When various mechanisms in cancer causing cells show resistance towards one or many chemotherapeutics, it hinders the efficacy of chemotherapy. This is referred as multidrug resistance. There are several factors that contribute in MDR. This research specifically focuses on modulate resistance towards multiple drugs by co-delivery of the nanoparticle. This research review has highlighted several delivery systems of nanodrug for overcoming the mechanism followed by MDR. This is done by exploiting, evading or neutralizing the pumps of drug efflux. The research essay has specifically discussed five different system categories. These categories are Mdr-1 and survivin-targeting, Docetaxel and siRNA, Paclitaxel and curcumin, Doxorubicin and paclitaxel and Doxorubicin and PSC 833. Based on the overall discussion, a brief summary is provided. Keywords: Drug resistance, nanomedicine, co-delivery, drug delivery.

76-79

Authors: Shuosheng Zhang

This essay has discussed various ways by which two or more than two drugs have been combined with Camptothecin through nanoparticles in order to yield anti-cancer therapy effectiveness. A systematic and comprehensive literature review has been prepared to show such combinations demonstrated high anticancer efficacy.

84-86

Authors: Xiaochai Zhu

Poly lactic-co-glycolic acid (PLGA) based nanoparticles are wildly used for the delivery of bioactive compounds such as dexamethasone, curcumin, azithromycin, doxorubicin and indocyanine green. It was found that those polymeric compounds can be effectively used for nanoparticle drug delivery. They are more biocompatible and lesser resistant in the case of targeted drug delivery. These are observed to have wide-ranging applications. Many of the PLGA polymers are being currently under research for commercial use and treatment. They have many fabrication techniques. It is imperative to understand their limitations in the future. There is a need for more research to overcome these limitations to develop drugs that are more efficient.

92-97

Authors: Pavan Kumar Kandula, Srinivasa B Rao, K Sangeetha, YJV Reddy, Sai Krishna Gudi

Background: The quality of life can be improved by enhancing the standards of the medical treatment at all levels of the healthcare delivery system. A medical audit oversees the observance of these standards. Prescription Audit offers the most comprehensive overview of performance, detailing parameter as per the check list of prescription audit. Aim: To monitor, evaluate and suggest modifications (if necessary) in the prescribing practices of medical practitioners. Methods: The observational study was conducted over a period of 6 months and data were collected from 1093 prescriptions collected from outpatient department of a tertiary care teaching hospital in India. Results: Total 1093 prescriptions were evaluated for the Audit, out of which 56.4% were Male & 43.6% were Female cases. Majority of the study subjects belonged to the age group of 40-59 years (32.4%). During the study mainly twelve parameter were assessed according to the checklist provided by the Hospital with total 1093 samples of prescription audit, only 2.2 % (280) cases had the non –compliance, 64.5% (8464) cases had compliance and 33.3% (4372) not applicable to this parameters. Conclusion: The results obtained from the study shows the prevailing prescribing habits at our institution. Many of the prescribing trends from this study are a cause of concern and need attention. This study reveals that the auditing of prescription in terms of rationality, it remains poor. The value of such audits in generating and testing hypotheses on inappropriate prescribing will definitely create an intervention to improve prescribing habits and ultimately patient care will be improved.

102-105

Authors: S Manvizhi, B S Mathew, Anil K Kuruvilla, Kalpana Margaret Ernest, Saravana Kumar, V Balaji, Vigil James, Denise Fleming

Objectives: To determine the percentage of neonates with sepsis, on treatment with standard recommended dose of intravenous ciprofloxacin, who had the serum ciprofloxacin Peak concentration: Minimum inhibitory concentration (Cmax:MIC), within the acceptable range. Design: Observational study design Intervention : In the Neonatology ICU, ciprofloxacin was initiated at a dose of 10mg/kg, twice daily in 95 neonates diagnosed with sepsis. On day 3 of ciprofloxacin, blood specimens were collected to measure the trough and peak concentrations of ciprofloxacin and was measured by high performance liquid chromatography. The MIC was measured if the blood culture was positive. When the blood culture was negative,the reference values for the MIC from ‘The Clinical and Laboratory Standard Institute Guidelines’ were adopted. Main outcomes: Minimum inhibitory concentration and serum concentrations of ciprofloxacin Results: Blood culture was positive in 14 babies. The mean (±SD) trough concentration of ciprofloxacin in term, preterm and very preterm neonates was 3.21(±1.99), 2.54 (±1.26) and 4.01(±1.80) μg/mL respectively. The mean (±SD) peak concentration of serum ciprofloxacinin term, preterm and very preterm neonates was, 12.55 (±4.945) 8.68(±3.61) and 12.07(±3.63) μg/mL, respectively. The percentage of neonates who achieved the acceptable Cmax /MIC ratio was predicted to be 74.07% if the strain was sensitive, 7.41% if intermediate and zero for resistant strains. Conclusion: The current recommended dose of intravenous ciprofloxacin in neonates in India may be adequate for treating sepsis due to susceptible organisms. For the treatment of sepsis caused by organisms with intermediate susceptibility, higher dosing regimens may be needed.

112-116

Authors: Mohammad Morshad Alam, Md. Mamun Or Rashid, Foysal Hossen, Kazi Nahid Akhter, Shajeda Akter Nishat, Abrar Wahab

Silver nanoparticles constitute a very promising approach for the development of new antibacterial systems. Nanoparticulate objects can bring significant improvements in the antibacterial activity of this element, through specific effect such as an adsorption at bacterial surfaces. In this study, polyaniline coated AgNPs-extract nanoparticles were investigated for their antibacterial activity. Silver nanoparticles were prepared by the reduction of silver nitrate and NaBH4 was used as reducing agent. Silver nanoparticles and extracts were mixed thoroughly and then coated by polyaniline. Prepared nanoparticles were characterized by Visual inspection, Ultraviolet-visible spectroscopy (UV), Fourier transform infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM) techniques. Antibacterial activities of the synthesized silver nanoparticles were tested against Antibacterial activities of the synthesized Ag-Extract nanoparticles were tested against Staphylococcus aureus ATCC 25923, Salmonella typhimurium ATCC 14028, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. UV–Vis spectrum of reaction mixture showed strong absorption peak with centering at 400 nm. The FT-IR results imply that Ag-NPs were successfully synthesized and capped with bio-compounds present in Momordica charantia. SEM results revealed that the particle size of these combined nanoparticles was 78.5 to 100 nm in most cases. In most of the cases, Ag-Extract NPs showed better antibacterial activity in compared to our control ciprofloxacin. The result revealed that Ag-extract NPs showed 28±0.68, 8±0.30, 35±0.48, 27±0.35mm zone of inhibition against for S. aureus, S. typhi, E. coli, P. aeruginosa respectively, whereas ciprofloxacin (positive control) showed 23±0.40, 21.40±0.40, 26.18±0.40, 25.32±0.40 mm zone of inhibition for these selected strains. Further studies should be undertaken to elucidate the exact mechanism of action by which AgNPs-extracts exert their antimicrobial effect which can be used in drug development program for safe health care services.

127-130

Authors: Rajesh K Maheshwari, Rashmi Dahima

As per the mixed solvency concept, every substance present in this universe has got solubilizing power. The substance may be a gas, liquid or solid. The present research work is an attempt to demonstrate the solubilizing property of solids. Also, the present research work is one of the examples which prove that solids can also be employed for spectrophotometric analysis of poorly soluble drugs in place of organic solvents. Tinidazole has got poor solubility in distilled water, while, significantly high solubility in a eutectic liquid of two solids, namely, phenol and lignocaine hydrochloride. Phenol and lignocaine hydrochloride were employed in 4:1 ratio to give eutectic liquid (PL 41). This eutectic liquid was employed to act as solvent to extract out the drug, tinidazole, from the fine powder of its tablets for spectrophotometric estimation at 318 nm. Necessary dilutions were done using distilled water. The solubility of tinidazole in distilled water is 5.38 mg/ml at room temperature while the approximate solubility in PL 41 is more than 200 mg/ml. Proposed method is novel, accurate, rapid and free from toxicity of organic solvents and reproducible. Recovery studies and statistical data proved the accuracy, reproducibility and precision of the analytical method employed. Tablet excipients together with phenol and lignocaine hydrochloride did not interfere at 318 nm.