DARU, Journal of Pharmaceutical Sciences
Volume:19 Issue: 1, 2011

Background and purpose of the study: Herbal enhancers compared to the synthetic ones have shown less toxis effects. Coumarins have been shown at concentrations inhibiting phospoliphase C-Y (Phc-Y) are able to enhance tight junction (TJ) permeability due to hyperpoalation of Zonolous Occludense-1 (ZO-1) proteins. The purpose of this study was to evaluate the influence of ethanolic extract of Angelica archengelica (AA-E) which contain coumarin on permeation of repaglinide across rat epidermis and on the tight junction plaque protein ZO-1 in HaCaT cells. Transepidermal water loss (TEWL) from the rat skin treated with different concentrations of AA-E was assessed by Tewameter. Scanning and Transmission Electron Microscopy (TEM) on were performed on AA-E treated rat skin portions. The possibility of AA-E influence on the architecture of tight junctions by adverse effect on the cytoplasmic ZO-1 in HaCaT cells was investigated. Finally, the systemic delivery of repaglinide from the optimized transdermal formulation was investigated in rats. The permeation of repaglinide across excised rat epidermis was 7-fold higher in the presence of AA-E (5% w/v) as compared to propylene glycol:ethanol (7:3) mixture. The extract was found to perturb the lipid microconstituents in both excised and viable rat skin, although, the effect was less intense in the later. The enhanced permeation of repaglinide across rat epidermis excised after treatment with AA-E (5% w/v) for different periods was in concordance with the high TEWL values of similarly treated viable rat skin. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. Treatment of HaCaT cell line with AA-E (0.16% w/v) for 6 hrs influenced ZO-1 as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in Confocal Laser Scanning Microscopy studies (CLSM) studies. The plasma concentration of repaglinide from transdermal formulation was maintained higher and for longer time as compared to oral administration of repaglinide.Major Results suggest the overwhelming influence of Angelica archengelica in enhancing the percutaneous permeation of repaglinide to be mediated through perturbation of skin lipids and tight junction protein (ZO-1).

Background and the purpose of the study: Biodegradable Poly(caprolactone fumarate) (PCLF) has been used as bioresorbable sutures. In this study, doxorubicin HCl (Dox) loaded PCLF nanoparticles were prepared and characterized. PCLFs were synthesized by polycondensation of PCL diols (Mws of 530, 1250 and 2000) with fumaryl chloride. The degradation of PCLF in NaOH, water and phosphate buffer saline (PBS), was determined in terms of Mw. Nanoparticles (NPs) were prepared by two methods. In microemulsion polymerization method, dichloromethane containing PCLF and photoinitiator were combined with the water containing surfactants and then placed under light for crosslinking. In nanoprecipitation method, the organic solvent containing PCLF was poured into the stirring water. The effect of several variables concentration of PCLF, poly vinyl alcohol (PVA), Dox and Trypan blue (Trb) and the Mw of PCLF and PVA) on NP size and loading were evaluated. PCLF 530, 1250 and 2000 in PBS or water were not degrade over 28 days. Nanoprecipitaion method gave spherical (revealed by SEM images) stable NPs of about 225 with narrow size distribution and a zeta potential of -43 mV. The size of NP increased significantly with increase in Mw or concentration of PCLF. Although PVA was not necessary for formation of NPs but decreased the NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing the drug concentration, increased the drug loading (DL) and NP size. The entrapment efficiency (EE) for Trb ranged from 1% for PCLF530 to 6% for PCLF2000. An increase in PCLF concentration resulted in an increase in EE. Dox and Trb release showed a burst followed by 80% and 78% release during 3 and 4 days respectively. PCLF possessed suitable characteristics for preparing nanoparticulate drug delivery system including desired NP size, stability and degradation time. Although PCLF530 NPs were the smallest, their DL was lower than PCLF1250 and 2000 NPs.

Background and the purpose of the study: Domperidone (DOM) is a dopamine- receptor (D2) antagonist, widely used in the treatment of motion-sickness. The pharmacokinetic parameters of DOM make it a suitable candidate for development of Solid Lipid Nanoparticle (SLN) and Nanostructured Lipide Carrier (NLC). The purpose of the present investigation was to prepare and evaluate DOM loaded solid lipid nanoparticles (DOM-SLN) and DOM loaded nanostructured lipid carriers (DOM-NLC). DOM loaded SLN and NLC were prepared by hot homogenization followed by ultrasonication technique, using trimyristin as solid lipid, cetyl recinoleate as liquid lipid and a mixture of soy phosphatidylcholine (99%) and tween 80 as surfactant. SLN and NLC were characterized for particle size, polydispersity index (PDI), zeta potential and entrapment efficiency. The effects of composition of lipid materials and surfactant mixture on the particle size, PDI, zeta potential, drug entrapment efficiency, and in vitro drug release behavior were investigated. DSC analysis was performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by transmission electron microscopy (TEM). SLN and NLC formulations were subjected to stability study over a period of 40 days. The mean particle size, PDI, zeta potential and entrapment efficiency of optimized SLN (SLN1) and NLC were found to be 30.45 nm, 0.156, 12.40 mV, 87.84 % and 32.23 nm, 0.160, 10.47 mV, 90.49 % respectively. DSC studies revealed that DOM was in an amorphous state and triglycerides were in the β prime form in SLN and NLC. Shape and surface morphology was determined by TEM revealed fairly spherical shape of nanoparticles. In vitro release studies demonstrated that both the SLN and NLC formulations possessed a controlled release over a period of 24 hrs. SLN and NLC formulations were subjected to stability over a period of 40 days. There was no significant (P < 0.05) change in particle size, zeta potential, PDI and entrapment efficiency indicating the developed SLN and NLC were fairly stable. Fairly spherical shaped, stable and controlled release DOM-SLN and DOM-NLC could be prepared by hot homogenization followed by ultrasonication technique.

Background and the purpose of the study: The objective of the present work was to improve bioavailability of cepodoxime proxetil through gastroretentive microballoon formulation. Microballoons of cefpodoxime proxetil were formulated by solvent evaporation and diffusion method employing hydroxypropylmethyl cellulose (HPMC) and ethyl cellulose (EC) polymers and characterized for particle size, surface morphology, incorporation efficiency, floating behavior, in vitro drug release study and differential scanning calorimetry (DSC). The average particle size of formulated microballoons was in the range of 54.23±2.78-95.66±2.19µm. Incorporation efficiencies of over 83.77±0.85 % were achieved for the optimized formulations. Most of formulations remained buoyant (having buoyancy percentage maximum of 81.36±1.96%) for more than 12 hrs indicating good floating behavior of microballoons. Higher values of correlation coefficients were obtained with Higuchi's square root of time kinetic treatment heralding diffusion as predominant mechanism of drug release. Inferences drawn from in vitro studies suggest that microballoons may be potential delivery system for cefpodoxime proxetil with improvement in bioavailability in comparison to conventional dosage forms.

Background and the purpose of the study:Layer-by-layer (LbL) deposition of polyelectrolytes (PEs) has received a great attention in the area of drug delivery due to its simplicity and versatility. This research was aimed to develop multilayered microcapsules through LbL deposition of chitosan (CHI) and sodium alginate (NaALG) and utilize them as vehicle for controlled delivery of isoniazid (INH). CaCO3 particles, prepared by colloidal crystallization of CaCl2 and Na2CO3 solutions, were used as micro-templates for LbL deposition of CHI and NaALG. Subsequent to the deposition, templates were decomposed to obtain hollow microcapsules. Prepared microcapsules were subjected to physicochemical evaluations, drug release and stability studies.Results and major Though CaCO3 particles possessed a rough and irregular surface, prepared hollow microcapsules were spherical in shape, having smooth surface and regular thickness. Following deposition of each layer, alternating values of zeta potential were observed, indicating the formation of multilayered films. Microcapsules with 5 bilayers, i.e. (CHI/NaALG)5 provided 39% entrapment efficiency and exhibited a controlled release behavior, lasting up to 24 hrs. An improvement in drug release rate and stability profile of the formulation was observed by increasing the number of deposition steps and performing the crosslinking of polyelectrolytes. This study showed that the prepared formulation could promisingly be utilized as controlled delivery vehicle for INH.

Background and the purpose of the study:Multiparticulates by powder layering process have advantages of the uniform distribution of the binder solution, easy-to-clean pan and the possibility of applying the successive functional film coating using the same equipment. This study relates to a multiparticulate formulation comprising pellets with a multilayer of pectin-ethyl cellulose on non pareil seeds by powder layering technology. The pellets were prepared to target ketoprofen in colon based on the microbial enzyme dependent drug release mechanism. Multiparticulate formulation by powder layering technology was prepared by conventional pan coating process to evaluate the effect of 59% methoxylated pectin and 45 cps ethyl cellulose on coating label. The formulations were tagged with 99mTc-DTPA, a tracer in gamma scintigraphy study to evaluate the transit behavior of drug loaded pellets and compared with uncoated pellets to evaluate its specific release. The transit behavior and scintigraphy image clearly indicates that the formulation can delay the drug release prior to colon. In albino rabbit, the coated pellets released drug in the colon indicating that site specificity has been achieved with pectin/ethyl cellulose coating at 1:2 ratio with 20% coating label.Major Formulation containing pectin and ethyl cellulose with suitable coating label may be suitable as a coating formulation for colon delivery of ketoprofen and can be successfully evaluated by gamma scintigraphy method.

Background and the purpose of the study: Lovastatin is an antihyperlipidemic agent which has low bioavailability due to the extensive first pass metabolism. It was sought to increase gastric retention of lovastatin by development of a sustained release gastroretentive drug delivery system leading to reduced fluctuation in the plasma concentration and improved bioavailability. Floating microspheres were prepared by emulsion solvent diffusion technique, using various polymers and their blends. The in vitro performance was evaluated for drug-polymer compatibility, percent yield, particle size, drug entrapment efficiency, in vitro onset and duration of floatation, in vitro drug release as well as in vivo determination of serum cholesterol level. The mean particle size of microspheres was observed to be between 6.9 to 9.5 μm and the maximum particle size was around 50 μm. In vivo studies of the selected batches indicated lower level of serum cholesterol compared to the marketed tablet at the same dose but was not significant.Major The data obtained in this study suggested that a microparticulate floating dosage form of lovastatin can be successfully designed to yield controlled delivery with improved therapeutic efficacy.

Background and the purpose of the study: Diabetic neuropathy is the most common diabetic complication that often is accompanied by significant morbidity, mortality and economic burden. The purpose of this study was evaluation of effect of Semelil (ANGIPARSTM), a new herbal drug for treatment of diabetic foot ulcers or diabetic peripheral neuropathy. In this double blind clinical trial, 49 type 2 diabetes patients with different degrees of neuropathy were evaluated in two groups (ANGIPARSTM and placebo groups). All patients were assessed at the start and 12 weeks after treatment, with laboratory tests, United Kingdom screening test, Michigan neuropathy screening score, Michigan diabetic neuropathy score, vibration perception thresholds, nerve conduction study, monofilament test and visual analog scale. Michigan diabetic neuropathy score was decreased notably in ANGIPARSTM group. In the nerve conduction study, appropriate meaningful changes were observed in the distal latency and amplitude in the motor Ulnar nerve in ANGIPARSTM group. The results showed limited evidence of efficacy of ANGIPARSTM in diabetic neuropathy treatment and more studies with a larger sample size and longer duration are required.

Background and the Purpose of the Study: Patients undergoing high-dose chemotherapy for hematological malignancies are susceptible to development of oral mucositis, and no effective modality has been reported for its prophylaxis and treatment. The aim of this study was to evaluate the effectiveness of zinc mouthwash on chemotherapy-induced oral mucositis lesions. In this double-blind randomized trial, patients under chemotherapy for acute leukemia were divided into two test and control groups of 15 patients each. The groups were homogeneous with respect to medical history, tumor characteristics, and therapeutic details. The test group received 10ml 0.2% zinc sulfate mouthwash, and the control group received 10ml 0.2% chlorhexidine gluconate mouthwash, twice a day for a period of two weeks. Spijkervet scale was used to grade the severity of mucositis at every other week during eight weeks. The severity scores were analyzed with repeated measure ANOVA using SPSS 13.0 computer software. Mean severity scores were generally lower in the test group compared to the controls at all four time intervals evaluated; but only, the differences in weeks of 2 and 3 were statistically significant (P=0.025). Zinc mouthwash used in conjunction with chemotherapy may reduce the severity of oral mucositis lesions in patients with leukaemia.

Background and the purpose of the study: Stelleropsis antoninae Pobed. (Family: Thymelaeaceae) grows wildly as an herbaceous plant in Iran. Most of the Thymelaeaceous plants contain lignans and neolignans, which have important pharmacologically properties. In the present study, the isolation and identification of the main lignans and neolignans of S. antoninae, which has not been previously reported is described and compared to other species. Column (CC) and High Performance Liquid Chromatographic (HPLC) methods were used for the isolation and purification, and 1H-NMR, 13C-NMR, HMBC, HMQC, H-H COSY and MS were employed for the identification of the compounds isolated from the methanol extract. From the methanol extract of the aerial parts of S. antoninae four lignans, syringaresinol (1), syringaresinol 4-O-β-D-glucopyranoside (4), syringaresinol 4-O- β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside (5), liriodendrin (6), and two neolignans, 5-methoxylariciresinol 4'-O-β-D-glucopyranoside (3) and dehydrodiconiferyl alcohol 4-O-β -D-glucopyranoside (2) were isolated and identified. Major The results of this study show that siringaresinol, a well-known bioavtive compound, and its glucosides are the main lignans, and lariciresinol and coniferyl alcohol derivatives are the main neolignans of S. antoninae.