JOURNAL OF DRUG DELIVERY AND THERAPEUTICS

9-22

Authors: mithun bhowmick

Designing and development of transdermal patches can be described as state of the art. The development of Transdermal drug delivery system is multidisciplinary activity that encompasses fundamental feasibility studies starting from the selection of drug molecule to the demonstration of sufficient drug flux in an ex vivo and in vivo model followed by fabrication of a drug delivery system that meets all the stringent needs that are specific to the drug molecule (physicochemical and stability factors), the patient (comfort and cosmetic appeal), the manufacturer (scale up and manufacturability) and most important the economy. The assessment of the performance of transdermal therapeutic devices designed for controlled drug release may result in a complex analytical issue and multidisciplinary studies focused on the evaluation of physicochemical, morphological and textural properties of the products may be required. This paper presents a review of transdermally applied formulations with emphasis on the evaluation of patches in a wide variety of evaluation parameters such as Physico-chemical evaluation, Adhesive evaluation, Skin irritation test, In-vitro, Ex-vivo, In-vivo techniques using animal models and human skin and Accelerated stability studies. Keywords: Transdermal patches, Physico-chemical evaluation, Adhesive evaluation, Skin irritation test, In-vitro, Ex-vivo and In-vivo techniques, Accelerated stability studies.

33-38

Authors: Seema Gautam, Arun Kumar Singh

The primary object of self-nanoemulsifying drug delivery system (SNEDDS) is to enhance the oral bioavailability of poorly water soluble drugs.The major problem in oral formulations is low and erratic bioavailability, which mainly results due to poor aqueous solubility of active constituents. Among various approach SNEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose. Nano-emulsions can be easily fabricated by low-energy emulsification methods, such as the phase inversion ,temperature method and phase inversion composition method. SNEDDS are anhydrous homogenous liquid mixtures consisting of oil, surfactant, drug and co-emulsifier or solubilizer, which spontaneously form oil-in-water nanoemulsion of approximately 200 nm or less in size upon dilution with water under gentle stirring. Keywords: Self emulsifying drug delivery system, surfactant, co-surfactant.

45-52

Authors: DHRUVKUMAR MITESHKUMAR SONI

The present report discusses about the clinical trial requirements for Friedreich ataxia disease such as inclusion and exclusion criteria for the patients,primary/secondary outcome measuresrequired for assessing the efficacy of therapies viarating scales, physical activity tests, biomarkersand number of subjects/patients to be enrolled in each phase of the clinical trials of Friedreich ataxia (F.A.). These parameters have been selected from the ongoing and completed clinical trials for F.A. as reported in Clinical trials.gov and Friedreich Ataxia Research Alliance (FARA) official website. A total of 33 clinical trialdetails werereviewed for compilation of the above mentioned parameters. For the purpose of this report, the most useful and most commonly assessedprimary/secondary outcome measureswith respect to efficacy as well as inclusion and exclusion criteria have been selected and are being cited in this review.The outcome measures for the purpose of efficacy trials can broadly be classified as primary and secondaryoutcome measures and in each category, subclasses are being presented in the order of their priority as determined by their usefulness and common occurrence in all trials mentioned. These outcome measuresincludeRating Scales for Friedreich Ataxia, Physical Activity Tests and Biomarkers, evaluation of Cardiac functionality viz. left ventricular wall mass, non-invasive measures of systolic and diastolic ventricular function, echocardiography and immunogenicity.The genetic predisposition of Friedreich ataxia (epigenetics) leading to the pathogenesis of the disease is also discussed in this report. Based on above primary and secondary outcomes measures and inclusion and exclusion criteria, a tabular representation of the ongoing/ completed clinical trials representing the efficacy studies of the test molecules and the patient involvements in each clinical trial is also been listed. Various aspects of clinical trialsneeded for assessing ataxic stage in Friedreich ataxia disease is been reviewed in this article. Key words:Friedreich ataxia, Friedreich Ataxia Research Alliance (FARA), Inclusion and Exclusion criteria, primary and secondary outcome measures, rating scales, biomarkers, physical activity tests.

58-67

Authors: Mohammed Abdul razack, G S Prasad

Rivastigmine, an Anti-Alzheimer’s drug suffer from a major limitation of sever GI adverse events such as nausea, vomiting, diarrhea, loss of appetite, weight loss and increase dosing frequency [1]. The present work aim at design, optimization and development of rivastigmine once a day controlled release formulation to minimize the above limitation and increase patient’s compliance. Based on the target in-vitro release profile derived from pharmacokinetic simulation [2], a once a day matrix tablet with the simulated dose was developed. The simple direct compression process was followed as a manufacturing process, the percentage of Polymer HPMC K100M, Polyethylene oxide (PEO WSR303) and insoluble excipients microcrystalline cellulose used in the formulation were optimized using 23 full factorial design. The formulations were then evaluated for the physical characteristics of blend, tablets, swelling index, percentage of erosion, drug release and release rate kinetic. The quadratic model was suggested, contour and 3D graphs were generated. The optimized formulation was subjected to stability studies. The final optimized formulation showed a comparative release profile similar to that the desired in-vitro target release profile, which followed zero order release kinetics and a stable formulation. Keywords: Controlled Release Formulation, Rivastigmine Tartarate, Anti-Alzheimer’s drug, HPMC K100M, Polyethylene oxide (PEO WSR303)

75-82

Authors: Gebremichael Lemlem Gebremedhin, P Gomathi

Objectives: To assess the extent and nature of drug utilization among pregnant women attending antenatal care in hospitals of Mekelle, Tigray, Ethiopia. Methods: Institution-based cross sectional study was conducted by reviewing the antenatal care follow up cards and interviewing pregnant women using semi-structured questionnaire by nurses working in the four hospitals. Details of drugs self utilized and prescribed during the current pregnancy were investigated and categorized according to the United States Food and Drug Administration fetal risk classification. Data was analyzed using SPSS version 20.0. Result: Of the 400 participants, majority 199 (49.8%) were in age group of 26-36years. 38 (9.5%) and 8 (2%) have self utilized modern and herbal drugs, respectively. Majority 26 (59.1%) were analgesics. Most 32 (84.2%) of the self medicated modern drugs were from category C, followed by category B. Illiterates and secondary school complete participants have practiced self medication 3.7 times (AOR 3.65 (1.31, 10.20), p=0.014) and 4.03 times (AOR 4.03 (1.09, 14.96), p=0.038) more than the tertiary complete participants, respectively. Self medication use was 3.7 times more among non government employees than governmental employees (AOR 3.68 (1.11, 12.17), p=0.033). Forty one (10.2%) of the participants had chronic diseases where most 26 (39.4%) were from category C, followed by category D 17 (25.8%). Of all the participants, 249 (62.2%) consumed one or more prescription drugs, with 1.86±0.94 average number of drugs prescribed per pregnant women. Majority 190 (76.3%) were from category B, followed by category C 94 (37.8%), category A 53 (21.3%), category C/D 23 (9.2%), category D 22 (8.8%), category B/C 7 (2.8%), category A/C 3 (1.2%) and category X 1 (0.4%). One hundred one (40.6%) of the drugs were prescribed in Ayder referral hospital, followed by Mekelle 93 (37.3%), kalkidan 31 (12.4%) and Meskerem 24 (9.6%) hospitals. Majority of the drugs prescribed in each hospital were from category B (80 (32.1%), 71 (28.5%), 21 (8.4%) and 18 (7.2%), respectively. Antibacterial drugs were the most commonly prescribed 146 (38.7%). Conclusion: Majority consumed one or more prescription drugs. Most of them were from category B. Keywords: pregnancy, self medications, prescription drugs, US FDA fetal risk classification, Hospitals of Mekelle.

88-91

Authors: Sharath Chandra S P, Sharada Angatahally Chandrashekaraiah

Blood Brian Barrier (BBB) is a physiologically and metabolically significant membrane that enables and limits the uptake of specific molecules by the brain, thus preserving the homeostasis within the Central nervous System (CNS).All the Antipsychotic drugs are permeable across the BBB, however most of First/Second generation antipsychotic drugs employed in the medical field are known to be associated with Extrapyramidal symptoms (EPS). Hence our interest is devoted in the development of novel antipsychotic drugs that ameliorate psychosis with least frequency of EPS. In our previous study the newly synthesized molecules, 6-fluoro-3-(piperidin-4-yl) benzo[d]isoxazole derivatives (S1-S4) which have shown positive alterations in chemical properties and biological activities demonstrating significant neuroleptic properties. However possibility and efficiency of these synthesized molecules to penetrate through the Blood Brain Barrier will be of utmost importance to determine its treatment efficacy. In this line of investigation, in the present study, in silico and in vitro methods are employed to evaluate the permeability in comparison with that of standard antipsychotic drugs, Resperidone and Haloperidol. In vitro analysis was done by Parallel artificial Membrane Permeability Assay (PAMPA) in PBS, where in permeability of S2(8.3x10-6) and S3(6.6x10-6) molecules showed higher permeability than known standards Warfarin(1x10-6), Resperidone(2.3x10-6) and Haloperidol(3.5x10-6), and the molecules exhibited recovery above 50% and in silico studies also showed high permeability rate with all the synthesized molecules. Thus we can conclude that, all the synthesized molecules have the potential to develop into promising Antipsychotic drugs. Key words: Antipsychotics, Blood Brain Barrier, EPS, PAMPA, In silico

99-106

Authors: H Doddayya, Shrishailgouda S Patil, G Ramya Sree, H Waseem, RH Udupi

Objectives: The objectives of the present study is to design and evaluate fast dissolving films of lamotrigine using HP ß CD inclusion complexes with an aim to achieve rapid drug release thereby controlling the seizures in the shortest possible time. Design: Inclusion complexes of lamotrigine were prepared with hydroxypropyl β cyclodextrin (HP β CD) employing different methods to improve the solubility and mask the bitter taste of the drug. Fast dissolving films were prepared by incorporating the developed inclusion complexes and using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) as film forming agents and other suitable excipients by solvent casting method. Results: Inclusion complexes prepared by ultrasonication method resulted in better solubility and dissolution rate compared to other methods studied. The fast dissolving films prepared using inclusion complexes were found to be transparent and smooth in texture. The thickness, drug content, % moisture absorption and moisture loss, folding endurance and weight variation was found to be uniform. In vitro release profiles were inversely proportional to the polymer and directly proportional to superdisintegrant and plasticizer concentration. Optimized formulations (F8 and F12) were subjected for fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) which revealed the absence of any chemical interactions between the excipients of the formulation. The formulations were found to be stable without any significant changes during the stability studies carried out as per the ICH guidelines. Conclusion: The study revealed the successful development of fast dissolving films of lamotrigine with promising results thereby suggesting the possible use of the developed films in the rapid management of epileptic seizures. Keywords: Fast dissolving films; epilepsy; lamotrigine; inclusion complex; HPMC; PVA; physico-chemical characterization.

114-116

Authors: Kamran Mousavi Hosseini, Saleh Nasiri, Behzad Nazel Khosroshahi, Mohammadreza Tabatabaei

Due to short shelf life of platelet concentrate 3-5 days, long-term preservation of human platelets will greatly reduce the risk of their shortage. Lyophilization has been proved feasible approach for this purpose. We want to show that platelets can be preserved by freeze-drying them with loading buffer containing trehalose, a sugar found at high concentrations in organisms that naturally survive drying. Washed platelet samples in a concentration of 0.8-1x10 9 plt/mL in loading buffers containing trehalose at various concentrations were incubated at 37°C for 4 h. Platelets were lyophilized with optimized concentration of trehalose 40 mmol/L. The aggregation response of trehalose-loaded platelets was tested against collagen agonist (2.0 µg/ml). Our results showed that aggregation of PRP, resuspended platelet samples in loading buffers containing 10, 20, 30 and 40 mmol/L trehalose and rehydrated lyophilized platelet containing 40 mmol/L trehalose were measured versus collagen agonist by aggregometry instrument with the activity of 7.7%, 22.3%, 45.9%, 71.4% and 35.3% respectively. However, when the platelets lyophilized without trehalose, most of the platelets disintegrated during rehydration step, some fused with adjacent cells and formed an insoluble clump. We concluded that trehalose at the concentration of 40 mmol/L can improve platelet aggregation activity versus collagen agonist in the loading buffer or dried state. Keywords: Trehalose; collagen; lyophilized platelet; platelet aggregation

122-126

Authors: G Shitha, V.K KAMALA BHAI AMMA, G BABU, C.R. BIJU

Benzoxazole derivatives display broad spectrum of biological and pharmacological activities. The main objective of the present study was to explore newer molecules with potent biological activity like anticancer activity. Insilico screening was done and compound with no violation in Lipinski rule of five and good docking score are selected for wet lab synthesize. Benzoxazole derivatives were synthesized and are evaluated for invitro anticancer studies. Derivatives were synthesized using different benzaldehyde and anhydride derivative. The synthesized compounds were then established on the basis of IR, MASS and 1H NMR spectral data and screened for anticancer activity on Human breast cancer cell line (MCF-7). The derivative showed significant activity on cell line. Keywords: Benzoxazole, dihydrophthalazine, anticancer, MTT assay.