Technological Innovation in Pharmaceutical Research Vol. 5

Objective: Lansoprazole an proton pump inhibitor, degrades in acidic environment, hence protection of drug is done by coating the drug with enteric coating polymers. Lansoprazole is an acid liable drug which degrades at acidic pH of stomach. The aim and objective of the present study was to prepare enteric coated delayed release tablets of lansoprazole by using press coating technique.

Methods: Core tablets were prepared by direct compression and evaluated for their physico-chemical properties. Press coated tablets were formulated by using different combinations of ethyl cellulose, HPMC E15 and HPMC K4M as a coating layer. Core and coated tablets were optimized by dissolution studies. Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies were performed to know the compatibility of drug with various excipients. Surface morphology and uniformity of coat was evaluated by Scanning electron microscopy (SEM). Stability of optimized formulation was evaluated according to ICH guidelines.

Results: Among the various formulations F5 containing ethyl cellulose: HPMC E15 (10:90) and F9 containing ethyl cellulose: HPMC K4M (25:75) were optimized based on the better drug release within 8 h. DSC studies and FTIR studies revealed compatibility of drug with excipients. Obtained SEM photographs of tablets showed that the surface of core tablet is uniformly coated with coat by press coating. Stability studies showed that the formulations were stable.

Conclusion: As a result, delayed release press coated tablets developed in this study delivered lansoprazole in the intestine and protected the drug from degradation.

Background: Scoparia dulcis is an annual erect herb distributed throughout tropical and subtropical regions of India, America, Brazil, West Indies, and Myanmar. The whole plant is used for ailments like diarrhea, stomach-ache, kidney stones, kidney problems, and fever. Scoparia dulcis is a rich source of flavones, terpenes and steroids.

Objective: The objective of the present investigation is to study the antioxidant power of different extracts of Scoparia dulcis. Scoparia dulcis Linn belongs to the family Scrophulariaceae and have speculated medicinal properties.

Materials and Methods: The different extract of this plant were obtained by successive extraction with petroleum ether, chloroform and ethanol. These extracts (PEESD, CESD and EESD) were then taken for phytochemical screening using different chemical reagents. An in-vitro antioxidant study is carried out by using various antioxidant screening methods like estimation of total Phenolic compounds, reducing power, nitric oxide scavenging and superoxide ion scavenging activity the antioxidant activity of the extracts was related to their phytochemical composition in terms of polyphenol and carotenoid contents.

Results: The chloroform extract was found rich in phytochemical constituents and had the highest antioxidant activity in the different antioxidant systems.

Conclusion: Result shows PEESD, CESD and EESD have significant antioxidant activity. The antioxidant potential may be attributed to the presence of polyphenolic compound.

Objective: The objective of the present study was to evaluate the total phenolic (TPC) and flavonoid content (TFC) of five less utilized fruits such as Aegle marmelos, Spondias pinnata, Limonia acidissima, Averhoa carambola, Crescentia cujete and was compared with Phyllanthus emblica, (Amla) well known for its antioxidant activities. The natural antioxidants present in fruits reduce the level of oxidative stress. Total phenolic and flavonoid contents of samples were correlated with antioxidant activities like 1,1-Diphenyl-2-Picryl-Hydrazyl (DPPH) free radical scavenging assay, Ferric reducing antioxidant potential (FRAP) assay and total antioxidant capacity (TAC).

Methods: The total phenolic of each fruit extract were determined by the Folin-Ciocalteu method with some modifications and the total flavonoids were estimated by Aluminum trichloride colourimetric method. The DPPH antioxidant assay, The FRAP assay and TAC were determined spectrophotometrically.

Results: The total phenolics were expressed as mg/100g Gallic acid equivalent (mg GAE/100 gm) and the total flavonoids were expressed as mg/100g Quercetin equivalent (mg QE/100 gm). TPC was found to be maximum in Spondias pinnata with 142.16 mg GAE/100 gm where as TFC was maximum in Phyllanthus emblica with 91.1 mgQE/100 gm. DPPH radical scavenging activity was expressed n percentage(%), FRAP values expressed as mg/100g Ascorbic equivalent (AAE) and the total antioxidant activity was expressed as mg/100g Ascorbic equivalent. Maximum DPPH radical scavenging activity was shown by Spondias pinnata (93.75%), FRAP values were maximum in Phyllanthus emblica with 72.6 mg AAE/100 gm and total antioxidant capacity was found to be highest in Spondias pinnata (50.1 mg AAE/100 gm).

Conclusion: Spondias pinnata, an underutilized fruit, was found to be promising with antioxidant activities comparable to Phyllanthus emblica.

The aim of the present study was to develop and evaluate natural biodegradable microcapsules of zidovudine (AZT) by using colophony resin as microencapsulating agent. An industrially feasible emulsification-solvent evaporation method was used for preparation of different batches of microcapsules. The proposed system was evaluated in vitro for particle morphology, microencapsulation efficiency, production yield, micromeritic properties, release profile and release kinetics etc. Physico-chemical characteristics of AZT and AZT loaded microcapsules were evaluated by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and infrared spectroscopy (FTIR). The resin coated microcapsules were found to be spherical, discrete and free flowing. Microencapsulation efficiency was in a narrow range (91-97%) suggesting an identical distribution of drug in different batches. DSC and XRD results showed a partial modification in AZT’s solid state. Zidovudine release from optimized batches of resin coated microcapsules was slow and over 24 hours depending on the core: coat ratio. Drug release was found to be following Fickian diffusion mechanism. Wall thickness was found to be increasing with the increase in the resin concentration. The t_50% values of various formulated batches were found to be increasing with corresponding decrease in the permeability constant values. The resin coated microcapsules exhibited good controlled release characteristics and were found to be suitable for once a day oral controlled release product.

Excessive noise exposure can cause acoustic trauma by causing mechanical and metabolic (oxidative) stress to the inner ear structure (cochlea) (TA). Apoptosis and necrosis of cochlear hair cells are caused by oxidative stress, which is caused by a rise in free radical ROS/RNS in the organs of Corti. Oxidative stress was characterized by increasing of malondialdehyde (MDA), decreasing of glutathione peroxidase (GPx) enzyme, and abnormal otoacoustic emission value (refer). Defense mechanism toward oxidative stress was mediated by endogenous antioxidant enyzme (superoxide dismutase/SOD, catalase/CAT, and GPx). Cellular mechanism of glutation peroxidase mimetic was similar as GPx. Aim of this study was to determine the impact of glutathione peroxidase mimetic to glutathione peroxidase and malondialdehyde level in blood, also otoacoustic emission value on soldiers with risk of TA due to explosion of Howitzer 105 artillery weapon. The design of this study was clinical trial pre and post design, randomized, double blind and placebo controlled, on 34 new recruit soldiers in Artillery Academy of Indonesian Army, during the soldiers were trained to firing Howitzer 105 artillery weapon, from 7^th-10^th July 2014 in Cimahi and Batujajar. Subjects were divided into 2 groups, the exposure group (group given treatment) and control group. Exposure group was given glutathione peroxidase mimetic (Ebselen SPI 1005) 200mg, orally once daily during the training, meanwhile control group was given. Malondialdehyde and Glutathione Peroxidase level in blood, pure tone audiometry and otoacoustic emission value (DPOAEs) was measured from those two groups, before and after firing training. The data was analyzed using parametric and non parametric, with Number Needed to Treat (NNT, 95%CI) and significance value (p<0.05). The results of this study showed the number of acoustic trauma events in controle group based on pure tone audiometry test was 23.5%, exposure group was 0%, and based on DPOAEs test the controle group showed 47.1% abnormal/refer, exposure group showed 100% normally/pass, and this difference stastically significance (p<0.051). The group which was given Ebselen SPI 1005 showed increasing 82.4% erythrocyte GPx level (NNT, 95%CI=1.889 [1.1593.016]; p=0.004), showed increasing 88.2% plasma GPx level (NNT, 95%CI=1.417 [0.970-1.775]; p<0.001), decreasing 100% erythrocyte MDA level (NNT, 95%CI = 2.125 [1.335-3.987]; p=0.01), showed decreasing 94.1% plasma MDA level (NNT, 95%CI=2.125 [1.29-3.904]; p=0.01), and resulting 100% in normal/pass DPOAEs value (NNT, 95%CI = 2.125 [1.335-3.987]; p=0.01). Giving Ebselen SPI 1005 to soldiers at risk of acoustic trauma during the firing of a Howitzer 105 artillery weapon increased GPx levels in the blood, decreased MDA levels in the blood, and resulted in DPOAEs values that were regular (pass).

In this chapter, we used cimetidine (C) and cimetidine with malathion (M + C) to assess oxidative stress enzymes suggestive of liver damage in rats exposed to malathion (M) in a subchronic form. Cimetidine is a histamine H2-receptor antagonist that has been demonstrated to inhibit many CYP450 isoforms. Malathion, a commonly used organophosphorus insecticide, causes oxidative liver harm. We studied male Wistar rats weighing 200-250 g, exposed to malathion orally for 3 weeks (0.15 mg / kg /day, 2 mg / kg /day, 15 mg / kg /day) and cimetidine 10 mg / kg /day. Malathion affects susceptibility to oxidative stress and possibly    modifies the antioxidant defense capacity directly or indirectly. This study will provide alternate  clinical diagnoses and therapies for pesticide-induced liver illness, as well as focusing future investigations on oxidative stress in organophosphate-exposed patients and creating intervention techniques.

The essential oils of fifteen Eucalyptus species harvested from the Jbel Abderrahman and Korbous arboreta (North East Tunisia) were screened for their antibacterial activities by the agar disc diffusion method. The activity of the Eucalyptus essential oils varied significantly within species and within strains. Eighteen major components as identified by GC/FID and GC/MS were selected for a study of the chemical and biological activity variability. The main one was 1,8-cineole, followed by spathulenol, trans-pinocarveol, ?-pinene, p-cymene, globulol, cryptone, ?-phellandrene, viridiflorol, borneol, limonene and isospathulenol. The chemical principal component analysis identified five species groups and subgroups, where each group constituted a chemotype, however that of the values of zone diameter of the inhibition (zdi) identified six groups of Eucalyptus oils, characterized by their antibacterial inhibition ability. The strongest activity was shown by E. platypus oil against Enterococcus faecalis and by E. lamannii oil against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A correlation between the levels of some major components and the antibacterial activities was observed.

Objective: The objective of the present work was to formulate nano vesicular gel for transdermal delivery of Pioglita zone and investigate its anti-diabetic potential.

Methods: Transferosomes were prepared by conventional rotary evaporation method, using various combinations of soya phosphatidylcholine (SPC), edge activators and pioglitazone (PZ). The optimized batch showed vesicle size 128.2nm, polydispersity index (PDI) 0.107, zeta potential  -31.22mv and drug entrapment efficiency (EE) 75.99%.  It was further incorporated in Carbopol 934 base gel and the prepared gel was evaluated for morphology, spread ability, in vitro and ex vivo release study, kinetics study. Anti- diabetic activity was evaluated by streptozotocin (STZ) induced diabetes model and it showed 72.85% reduction in sugar level at the end of 12 h by drug loaded transferosomal gel whereas marketed formulation showed 67.63% reduction in sugar level at the end of 12 h respectively.

Conclusion: The present study revealed   the potential of transferosomes for successfully carrying PZ and demonstrated appreciable decrease in glucose levels after the induction of diabetes in wistar rats. The prepared system has shown enhanced delivery of PZ via skin.

Objective: Synthesis of N-1 Substituted Indolylchalcone Hybrids and evaluation of anti-angiogenic activity using Chorioallantoic Membrane (CAM) Assay. The present study suggests that N-1 substituted Indolylchalcone hybrids of 2-acetyl benzimidazole might be promising analogs of angiogenesis inhibitors to manage the uncontrolled neovascularization occurring during malignant tumor development.

Methods:  Claisen-schmidt reaction is used for the synthesis of 30 Indolylchalcone hybrids, it involves condensation of N-1 substituted indole-3-carboxaldehyde and N1 substituted 2-acetyl- benzimidazole. The phase transfer catalyst, green catalyst such as anhydrous potassium carbonate (K₂CO₃) and PEG-400 are used in the alkylation and arylation. All synthesized indolylchalcone hybrids were evaluated for their antiangiogenic activity by in-vivo-chorioallantoic membrane (CAM) assay method.

Results: The synthesized indolylchalcone compounds are evaluated. The morphometric study was carried out as described by Melkonian et al. (2002). The Compounds with code C-2, I-1, I-2 are showing more potent effect on dose dependent assay of CAM. The compounds with code C-1, C-3, E-1 to E-3, M-1 and M-5 shows the significant activity, however, though the compounds with code B-1, B-2 ,CL-1 and A-5 were showing  antiangiogenic effect at 0.1 µM, but does not show any significant activity on dose dependent assay of CAM .

Conclusion: The synthesized Indolylchalcones as shown in graph possess very good dose dependent anti-angiogenic activities. The potency of anti-angiogenetic activity shows that methyl >Ethyl>Cl-benzyl> Benzyl>Isobutyl. 2-acetyl benzimidazole analogs have possible future scope to develop as potent angiogenesis inhibitors.

The present study aimed to analyze the major chemical components in the flower buds, pedicels and leaves of Syzygium aromaticum by Gas-Chromatography Mass spectrometry technique. The major constituent is eugenol in all of   pedicels (79.75%), buds (74.12%) and leaves (51.03%). In addition to eugenol, other important components are Acetyleugenol, Caryophyllene, Humulene, Caryophyllene oxide. Eugenol has a wide range of medicinal value such as antibacterial, antifungal, antiviral, anti-cancerous, anti-diabetic, anesthetic and antioxidant activities.