Loratadine Research Articles

Comparison of effect of desloratadine citrate disodium tablets and loratadine dispersible tablets in treatment of patients with allergic rhinitis

Objective To compare the efficacy and adverse reactions of desloratadine citrate disodium tablets and loratadine dispersible tablets in treatment of patients with allergic rhinitis, and their influence on leukotriene B4(LTB4), interleukin-4(IL-4), interleukin-10(IL-10) and interferon gamma(INF-γ). Methods From June 2015 to June 2016, a total of 110 patients with allergic rhinitis in the Second People's Hospital of Cangnan County were selected and randomly divided into control group and observation group according to the digital table, with 55 cases in each group.The control group was given loratadine dispersible tablets, while the observation group was given desloratadine citrate disodium tablets.Both two groups were treated for 14 days.The clinical efficacy, adverse reactions and changes of LTB4, IL-4, IL-10, INF-γ levels before and after treatment were compared between the two groups. Results The total effective rate of the observation group was 94.5%, which was significantly higher than 80.0% of the control group(χ2=6.310, P 0.05). After 2 weeks of treatment, the levels of LTB4, IL-4, IL-10 and INF-γ in the observation group were (67.74±10.15)ng/L, (52.37±5.12)μg/L, (81.26±11.78)μg/L, (94.47±7.87)μg/L, respectively, which in the control group were (80.32±9.97)ng/L, (62.95±5.45)μg/L, (96.32±11.57)μg/L, (86.74±7.63) μg/L, respectively, there were statistically significant differences between the two groups(t=7.124, 5.262, 4.654, 3.718, all P<0.05). Conclusion Both desloratadine citrate disodium tablets and loratadine dispersible tablets can effectively treat patients with allergic rhinitis, improve the symptoms and physical signs, reduce the levels of LTB4, IL-4 and IL-10, increase the level of INF-γ, and the adverse reactions are less and slight, but the efficacy of desloratadine citrate disodium tablets is better than loratadine dispersible tablets. Key words: Rhinitis, allergic, seasonal; Desloratadine citrate disodium tablets; Loratadine dispersible tablets; Leukotriene B4; Interleukin-4; Interleukin-10; Interferon-gamma

Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer.

Pancreatic cancer (PC), currently the third leading cause of cancer-related deaths in the USA, is projected to become the second leading cause, behind lung cancer, by 2020. The increasing incidence, low survival rate, and limited treatment opportunities necessitate the use of alternative approaches such as chemoprevention, to tackle PC. In this study, we report significant synergistic chemoprevention efficacy for the first time from a low-dose combination of a classical antihistaminic drug, Loratadine (LOR) and a neutraceutical compound, Sulforaphane (SFN) using a self-microemulsifying drug delivery system (SMEDDS) formulation. The formulation was developed using Quality by Design approach (globule size, 95.13 ± 7.9nm; PDI, 0.17 ± 0.04) and revealed significant (p < 0.05) enhancement in the in vitro dissolution profile confirming the enhanced solubility of BCS class II drug LOR with SMEDDS formulation. The LOR-SFN combination revealed ~ 40-fold reduction in IC50 concentration compared to LOR alone in MIA PaCa-2 and Panc-1 cell lines respectively, confirming the synergistic enhancement in chemoprevention. Further, the nanoformulation resulted in ~ 7-fold and ~ 11-fold reduction in IC50 values compared to LOR-SFN combination. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDs with SFN shows significantly enhanced chemopreventive efficacy of PC.

Alarin in different human intestinal epithelial cell types.

Alarin (AL), a new member of the galanin family, has been localized in various CNS regions, mainly in rodents. Among other effects, it modulates food intake. Therefore, we analyzed the immunohistochemical distribution pattern of AL in human intestinal epithelia. Cryosections of 12 human bowel samples were immunohistochemically double-stained for AL and α-defensin 5 (αD; first set). Two further sets of sections were quadruple-stained either (second set) for AL, chromogranin (CG), synaptophysin (SY), and somatostatin (SO) or (third set) for AL, CG, Peptide Y (PY), and 5-hydroxytryptamine (5-HT). Slides were digitized and quantitative analysis of co-localization rates was undertaken. Small bowel: most of AL-positive cells (56%) were αD-positive Paneth cells located within the base of the crypts (first set). In the second set, about 27% of AL-labeled cells were co-reactive for SY and CG, likely representing entero-endocrine cells. In the third set, the largest subpopulation of AL-positive cells was not co-reactive for other markers applied (89%); most of them were likely Paneth cells. Large bowel: co-localization of AL with αD was not detected (first set). In the second set, AL was frequently co-localized with the other three markers applied (68%). In the third set, AL was frequently co-localized with 5-HT and CG (31%) as well as with PY and 5-HT (22%). Due to its presence in various enteroendocrine as well as Paneth cells, AL may be involved in different physiological and pathological processes.

Real Time Selective Monitoring of the Dissolution Behavior of Pseudoephedrine Sulfate and Loratadine in Their Binary and Ternary Dosage Form by Utilization of In-Line Potentiometric Sensor

An electro-analytical procedure was progressed for quantitative determination and monitoring the dissolution behavior of both cationic pseudoephedrine sulfate (PSE sulfate) and loratadine (LOR) drugs in their binary mixture with each other and ternary mixture with paracetamol (PAR) by in-line potentiometric analysis system without a need for pre-treatment or derivatization of the sample. This approach is performed by measuring continuously the increase in the generated emf over time by incorporating an in-site selective electrode for PSE sulfate and LOR fabricated utilizing polymeric membrane of poly (vinyl chloride) (PVC), tetraphenyl borate (TPB) and potassium tetrakis (4-chlorohenyl) borate (KTCPB) as a cation exchanger, Bis(2-ethylhexyl) sebacate and nitrophenyl octyl ether (NPOE), were utilized as plasticizers for determination of PSE sulfate and LOR, conjointly. The proposed sensors for both drugs exhibited stable and fast responses over wide PSE sulfate and LOR concentration range (2 × 10−5 to 2 × 10−2 mol/L regarding PSE sulfate while 1 × 10−5 to 1 × 10−2 mol/L regarding LOR). Afterwards, the proposed potentiometric method's validation was performed, and it is supposed to be eco-friendly and green technique in which consumption of solvents and sample pre-treatment were not mandatory for its application.

The Use of Nata de Coco Derived Bacterial Cellulose as a Potential Excipient for Directly Compressed Tablets

Nata de coco is produced through the fermentation of coconut water using Acetobacter xylinum bacteria. Chemically, Nata de coco is high in fiber, consisting of bacterially derived cellulose. Bacterial celluloses present a number of unique physical properties compared with plant celluloses including a relatively high purity and crystallinity, with mechanical strength. These properties lend Nata de coco to be extremely amenable to research. The current study attempts to assess the suitability of Nata de Coco derived bacterial cellulose in direct compression tablet formulation. Nata de coco, at various states of hydration, defined here as 0%, ‘low’ and ‘high’, achieved by both oven-drying and freeze-drying is incorporated into a low-dose loratadine powder blend for direct compression into tablets. The dissolution profile of these novel tablets were evaluated for release properties. The resulting tablets reveal freeze-drying, compared with oven-drying, markedly improve the properties of Nata de Coco for inclusion in a tablet formulation, producing tablets with improved disintegration times and dissolution profiles and retaining physical stability. Oven dried Nata de Coco, resulting in physically weaker tablets, with poor friability and hardness. The upper limit for water-content in both cases, similar to HPMC, appears to be 11%. Freeze-dried Nata de Coco therefore presents considerable promise for use as a tablet excipient to produce a rapid-release formulation.

Alpha-tocopherol acetate nasal spray in the treatment of pollen-induced allergic rhinitis

This study compared the effectiveness and tolerability of alpha-tocopherol acetate nasal spray (ATANS) to those of beclomethasone nasal spray (BNS) and loratadine (LT) for the treatment of pollen-induced allergic rhinitis. This active-controlled, patient-preference, observational trial lasted 7 days. Tested variables were nasal symptoms, endoscopic examination, additional medications, general effectiveness, safety, and tolerability. Of 116 patients, 63 patients decided to use ATANS, 32 BNS and 21 LT. During the treatment, the mean daily rhinitis symptom score decreased significantly in all groups. The 7‑day mean score in the ATANS group (0.98) was comparable to that of the BNS group (0.92) and significantly higher than that of the LT group (0.70, P < 0.05). After treatment, the endoscopic score was significantly lower in all groups; the reductions were significantly greater in the BNS and LT groups than in the ATANS group (BNS vs. ATANS: P < 0.01; LT vs. ATANS: P < 0.05). Additional medications were not used by 60% (ATANS), 47% (BNS) and 95% (LT) of patients; the difference between ATANS and LT was significant (P < 0.01). Treatment was assessed as good or very good by 56% (ATANS), 69% (BNS) and 86% (LT) of patients; the differences between ATANS and BNS (P < 0.05) as well as between ATANS and LT (P < 0.01) were significant. Most patients (96%) did not experience any adverse events. Pollen intensity was comparable between groups and decreased marginally on day 7. ATANS can be considered an effective symptomatic treatment for patients with allergic rhinitis who wish to avoid side effects of antihistamines and corticosteroids. German “Register Klinischer Studien” (Reference number: DRK9338)

Production of Loratadine drug nanoparticles using ultrasonic-assisted Rapid expansion of supercritical solution into aqueous solution (US-RESSAS)

Effects of the process parameters such as pressure (12–30 MPa), extraction temperature (308–338 K), nozzle length (1–7 mm), nozzle diameter (150–450 μm) and ultrasonic power (70 W/L at 20 kHz) on morphology and mean particle size of the nanoparticles were investigated. ANOVA results illustrated that, pressure and nozzle length imposed the most significant contributions into the production of smaller particles. The Loratadine (LOR) particles were observed to become nanosized from the original average size of 32.6 μm to the smallest average size of 123.6 nm and 26 nm through RESSAS and ultrasonic-assisted RESSAS (US-RESSAS), respectively. Dissolution rates were measured before and after the processes, indicating an enhancement of 3.5 folds after the US-RESSAS process. Results of the two methods showed a significant difference in the particle size distribution. This is the first report on the simultaneous application of RESSAS and ultrasonic in the production of drug nanoparticles.

Onset of Action of the Fixed Combination Intranasal Azelastine-Fluticasone Propionate in an Allergen Exposure Chamber

A fixed-dose combination of intranasal azelastine hydrochloride and fluticasone propionate (MP-AzeFlu) is the most effective treatment of allergic rhinitis, but its onset of action requires further investigation. To compare the onset of action of MP-AzeFlu with the free combination of oral loratadine (LORA) and intranasal fluticasone propionate (INFP). In this single-center, randomized, placebo-controlled, double-blind, double-dummy, 3-period crossover trial, allergic rhinitis symptoms were induced in asymptomatic patients by ragweed pollen challenge in an allergen environmental exposure chamber. Patients received single-dose MP-AzeFlu, LORA/INFP, or placebo and were monitored for 4 hours. The primary outcome was onset of action measured by total nasal symptom score (TNSS). Secondary measures were total ocular symptom score (TOSS), total score of the 7 nasal and ocular symptoms (T7SS), and the global visual analog scale (VAS). The full analysis set included 82 patients, of which 78 completed all treatments. TNSS was significantly reduced versus placebo from 5 minutes for MP-AzeFlu and 150 minutes for LORA/INFP onward (both P < .05) till the end of assessment (0-4 hours). MP-AzeFlu reduced TNSS to a greater extent at each time point from 5 to 90 minutes (P < .05) and over the entire assessment interval (P ≤ .005) versus LORA/INFP or placebo. No statistically significant difference between LORA/INFP and placebo was observed over the assessment interval (P= .182). The onset of action of MP-AzeFlu assessed by TOSS, T7SS, and VAS was 10 minutes, 2 hours earlier than with LORA/INFP. MP-AzeFlu had a more rapid onset of action (5 minutes) and was more effective than LORA/INFP.

Dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs

BackgroundDengue virus (DENV) is an increasing global health threat and associated with induction of both a long-lived protective immune response and immune-suppression. So far, the potency of treatment of DENV via antiviral drugs is still under investigation. Recently, increasing evidences suggest the potential role of microRNAs (miRNAs) in regulating DENV. The present study focused on the function of miRNAs in innate insusceptible reactions and organization of various types of immune cells and inflammatory responses for DENV. Three drugs were tested including antiviral herbal medicine ReDuNing (RDN), Loratadine (LRD) and Acetaminophen.ResultsBy the microarray expression of miRNAs in 165 Patients. Results showed that 89 active miRNAs interacted with 499 potential target genes, during antiviral treatment throughout the critical stage of DENV. Interestingly, reduction of the illness threats using RDN combined with LRD treatment showed better results than Acetaminophen alone. The inhibitions of DENV was confirmed by decrease concentrations of cytokines and interleukin parameters; like TNF-α, IFN-γ, TGF-β1, IL-4, IL-6, IL-12, and IL-17; after treatment and some coagulants factors increased.ConclusionsThis study showed a preliminary support to suggest that the herbal medicine RDN combined with LRD can reduce both susceptibility and the severity of DENV.

A patient with anaphylaxis to diphenhydramine without cross-reactivity to loratadine

A patient with anaphylaxis to diphenhydramine without cross-reactivity to loratadine

Combining thioridazine and loratadine for the treatment of gastrointestinal tumor.

In 2015, the American Society of Clinical Oncology announced that strategies of using combination therapies have been indicated to be effective against many types of cancer. In the present study, thioridazine (THZ) was used in a combination therapy with loratadine (LOR) to target gastrointestinal tumor, with the aim of investigating whether combined therapy was superior to monotherapy in its antitumor effects. The antiproliferative effects on CT26.WT and MFC cells were analyzed using cell-counting kit-8 assay, and synergistic effect was assessed by combination index (Fig. 1). Annexin V and propidium iodide staining indicated the combination therapy was able to induce apoptosis and that this may be mediated via caspase-3, −9 and poly (ADP-ribose) polymerase (PARP) (Fig. 2). Antitumor activity was also evaluated in CT26.WT xenografts in BALB/c mice (Fig. 3). Furthermore, as expected, combination therapy was able to successfully inhibit the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signaling pathway (Fig. 4). These findings suggest that the combination therapy with THZ and LOR may provide a promising therapy for gastrointestinal cancer.

Self microemulsifying particles of loratadine for improved oral bioavailability: preparation, characterization and in vivo evaluation

The objective was to study the phase behavior of different formulations, to identify the micro emulsion area and to prepare solid SMEDDS particles (SSMED) of loratadine (LOR) for improving oral bioavailability (BA). Formulations were prepared with either Lauroglycol 90 or Peceol as oils, Solutol HS15 as surfactant and Transcutol P as co-surfactant. Then water titrations were done to know the phase behavior to identify microemulsion zone. The SSMEDs were prepared by physical adsorption on novel silicon based porous particulate carriers. The flow properties of SSMEDs were studied. SSMED with syloid XDP (SSMED-XS) was optimized based on the free flowing nature. The optimized formulation was evaluated for self microemulsifying efficiency, size, PDI, Zeta potential (ZP), robustness in different pH conditions, surface morphology and in vitro release studies. Further, the pharmacokinetic (PK) behavior of SSMEDs was evaluated in wistar rats. The optimized L-SMEDDS formulation possessed a mean globule size of 140.90 ± 2.01 nm. Stearyl amine at 1% level was added as positive charge inducer. The PXRD and SEM studies indicated loss of crystallinity of the drug. In vitro % drug release for LOR powder was 65% and for L and SSMED was ranging in between 95–99% in 2 h. The BA of SSMED with stearyl amine (SSMED-XS) was 2.28 fold (p < 0.05); S-SMEDDS without stearyl amine (SSMED-X) was 1.78 fold (p < 0.001) more, when compared with plain LOR suspension. Cationic SSMEDs showed significant difference over negatively charged SSMED during in vivo studies. The SSMED-XS was found to be stable upto 3 months at room temperature (RT).

Loratadine in combination with desloratadine for the treatment of chronic spontaneous urticaria in children: a clinical observation

Objective To evaluate clinical efficacy and safety of loratadine combined with desloratadine in the treatment of chronic spontaneous urticaria (CSU) in children. Methods A total of 177 children with CSU were enrolled into this study, and randomly and equally divided into 3 groups: combination group treated with an age-based dose of desloratadine tablet every morning and a weight-based dose of loratadine tablet before sleep every night for consecutive 28 days, loratadine group treated with a half tablet of placebo (starch tablet) every morning and oral loratadine tablet before sleep every night for consecutive 28 days, and desloratadine group treated with a half tablet of placebo (starch tablet) every morning and oral desloratadine tablet before sleep every night for 28 consecutive days. Possible adverse reactions were observed and recorded after the start of treatment, and therapeutic effects were evaluated at the end of treatment. Results A total of 166 patients completed the trial, including 55 in the combination group, 56 in the loratadine group and 55 in the desloratadine group. After 28-day treatment, the total response rate was significantly higher in the combination group (90.9%, 50/55) than in the loratadine group (71.4% [40/56], χ2 = 6.865, P 0.05). Conclusion Combination of loratadine and desloratadine was superior to loratadine or desloratadine alone in the treatment of childhood CSU, and there was no significant difference in the incidence of adverse reactions among the 3 treatment groups. Key words: Urticaria; Loratadine; Randomized controlled trials; Child; Desloratadine

Loratadine bioavailability via buccal transferosomal gel: formulation, statistical optimization, in vitro/in vivo characterization, and pharmacokinetics in human volunteers

Loratadine (LTD) is an antihistaminic drug that suffers limited solubility, poor oral bioavailability (owing to extensive first-pass metabolism), and highly variable oral absorption. This study was undertaken to develop and statistically optimize transfersomal gel for transbuccal delivery of LTD. Transfersomes bearing LTD were prepared by conventional thin film hydration method and optimized using sequential Quality-by-Design approach that involved Placket–Burman design for screening followed by constrained simplex-centroid design for optimization of a Tween-80/Span-60/Span-80 mixture. The transferosomes were characterized for entrapment efficiency, particle size, and shape. Optimized transferosomes were incorporated in a mucoadhesive gel. The gel was characterized for rheology, ex vivo permeation across chicken pouch buccal mucosa, in vitro release, and mucoadhesion. Pharmacokinetic behavior of LTD formulations was investigated in healthy volunteers following administration of a single 10-mg dose. Optimal transferosomes characterized by submicron size (380 nm), spherical shape and adequate loading capacity (60%) were obtained by using quasi-equal ratio surfactant mixture. In terms of amount permeated, percentage released, and mucoadhesion time, the transferosomal gel proved superior to control, transferosome-free gel. Bioavailability of the transferosomal gel was comparable to Claritin® oral tablets. However, inter-individual variability in Cmax and AUC was reduced by 76 and 90%, respectively, when the buccal gel was used. Linear Correlation of in vitro release with in vivo buccal absorption fractions was established with excellent correlation coefficient (R2>0.97). In summary, a novel buccal delivery system for LTD was developed. However, further clinical investigation is warranted to evaluate its therapeutic effectiveness and utility.

Formulation of Novel Glycerin Nanoparticles for Enhancement the Solubility of Loratadine; Application to Transdermal Hydrogel Delivery System

Owing to its slightly aqueous solubility, loratadine (LOR) is used in high doses in different marketed formulations to achieve its desirable bioavailability. The aim of this work is to formulate novel LOR-glycerin nanoparticles (LOR-GNPs) to increase LOR bioavailability. LOR-GNPs were prepared by a precipitation method and then evaluated for such size and morphology using dynamic scattering spectroscopy (DLS) and scanning electron microscopy (SEM), as well as the percentage entrapment efficiency (EE%) of free LOR from GNPs formulations was performed using titration method. Furthermore, the GNPs were formulated in hydrogel. The hydrogel viscosity, spreadability, homogeneity and abdominal rat skin permeation were studied and optimized DLS indicated a successful coating of LOR with glycerin surface that recorded an average size of 334 ± 30 nm with uniform particle size, while SEM showed LOR-NPs in different shapes. The EE% free LOR was found to be satisfactory with a mean content of 98.1 ± 0.3 and a relative standard deviation below 2.0% indicates the reproducibility of the LOR release. LOR-GNPs were formulated as a hydrogel to check their suitability for a dosage form usage. The hydrogel showed accepted viscosity, spreadability, and homogeneity. The results proved that the GNPs penetrated abdominal rat skin. The obtained results showed that LOR-GNPs are considered a new addition for improvement of LOR solubility when applied as a hydrogel. The developed method could be used for different insoluble candidates.

Suppressive Activity of Histamine H1 Receptor Antagonists, Desloratadine and Levocetirizine, on the Production of Periostin from Nasal Epithelial Cells In vitro

Background: Periostin, a 90-kDa endogenous extracellular matrix protein, is well known to be involved in the development and persistence of allergic rhinitis. Although histamine H1 receptor antagonists are recommended as first choice of agents in the treatment of allergic rhinitis, the influence of the agents on periostin production is not well understood. The present study was undertaken to examine the influence of histamine H1 receptor antagonists on periostin production from nasal epithelial cells after IL-4 stimulation in vitro. Methods: Human nasal epithelial cells (HNEpC) at a concentration of 1 × 105 cells/ml were stimulated with 10.0 ng/ml IL-4 in combination with either desloratadine (DLT), loratadine (LT), levocetirizine (LCT) or cetirizine (CT). After 48 h, culture supernatants were collected and assayed for periostin levels by ELISA. The influence of LCT on transcription factor, STAT6, activation and periostin mRNA expression were also examined by ELISA and real-time RT-PCR, respectively. Results: Treatment of cells with DLT, LT, LCT and CT suppressed the ability of HNEpC to produce periostin in response to IL-4 stimulation in dose-dependent manner. The minimum concentration that caused significant suppression is 0.01 mM for DLT, 0.05 mM for LT, 0.05 mM for LCT and 0.1 mM for CT. Treatment of HNEpC with LCT at more than 0.05 mM also suppressed STAT6 activation and periostin mRNA expression induced by IL-4 stimulation. Conclusion: The present results strongly suggest that histamine H1 receptor antagonists favorably modify the clinical conditions of allergic rhinitis through the suppression of periostin production from nasal epithelial cells after IL-4 stimulation.

Application of Successive and Progressive Spectrophotometric Resolution for the Analysis of Partially or Completely Overlapping Ternary Mixtures

In this work application of a recently developed progressive resolution technique and the well-established successive resolution techniques either separately or in combination for the analysis of ternary mixtures without prior separation steps. The resolution steps verified according to the degree of spectra overlapping either partially or completely. All the proposed spectrophotometric techniques consist of several consecutive steps utilizing ratio and/or derivative spectra. The proposed methods can be used for the determination of ternary mixture of pseudoephedrine sulphate (PSE), loratadine (LOR) and paracetamol (PAR). Pseudoephedrine (PSE) could be determined using successive one and applying zero crossing derivative ratio (DD1) at 218.6 nm and the derivative of the resolved spectrum of PSE and PAR at 217 nm and 235 nm via amplitude factor. Loratadine (LOR) could be analyzed either by constant center or dual wavelength (DWL) as well as progressively using their derivative spectrum by applying amplitude factor method at 261 nm and 305 nm without any contribution of PSE. Paracetamol (PAR) could be measured at its maxima at 248 nm either directly after resolution of LOR or via constant multiplication method. Moreover it could be analyzed using the first derivative of the mixture at 305 nm without any interference of others. Regression analysis showed good correlation in the concentration ranges 4-40 μg/mL, 3.5-35 μg/mL and 1.5-17 μg/ml for PSE, LOR and PAR, respectively. The specificity of the developed methods was investigated by analyzing laboratory prepared mixtures and was successfully applied for the analysis of pharmaceutical formulations containing the cited drugs with no interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with those of the official or reported methods of the cited drugs; using student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision.

Theoretical investigation of loratadine reactivity in order to understand its degradation properties: DFT and MD study.

Antihistamines are frequently used pharmaceuticals that treat the symptoms of allergic reactions. Loratadine (LOR) is an active component of the second generation of selective antihistaminic pharmaceutical usually known as Claritin. Frequent usage of this type of pharmaceuticals imposes the need for understanding their fundamental reactive properties. In this study we have theoretically investigated reactive properties of LOR using both density functional theory (DFT) calculations and molecular dynamics (MD) simulations. DFT study is used for collecting information related to the molecule stability, structure, frontier molecular orbitals, quantum molecular descriptors, charge distribution, molecular electrostatic potential surfaces, charge polarization, and local reactivity properties according to average local ionization energy surfaces. Based on these results, N24 atom of pyridine ring and oxygen atom O1 were identified with nucleophilic nature. In order to collect the information necessary for the proposition of degradation compounds we also calculated bond dissociation energies (BDE) for hydrogen abstraction and single acyclic bonds as well. According to BDE, the oxidation is likely to occur in the piperidine and cycloheptane rings. MD simulations were used in order to understand the interactions with water through radial distribution functions (RDF). Based on RDFs the most important interactions with solvent are determined for carbon atom C5, chlorine atom Cl15, and oxygen atom O1. Collected results based on DFT calculations and MD simulations provided information important for suggestion of possible degradation compounds. Covalent and noncovalent interactions between LOR and (•)OH have also been investigated.

Method Development for Quantification of Loratidine and Alverine Citrate by Visible Spectrophotometry

The present work describes on two colorimetric methods based on charge transfer complex reaction of loratidine (LRT) and alverine citrate (ALV) with chloranilic acid in chloroform. The methods were developed on Perkin Elmer LAMBDA 25 UV –VIS spectrophotometer with 1cm quartz cells. The methods were optimised to achieve maximum colour intensity and validated for reliability. The coloured complexes showed maximum absorbance at 538 nm for LRT and 540 nm for ALV. The absorbances were found to increase linearly with increase in concentration which was emphasised by the calculated regression coefficients (0.9998-0.9999). Linearity of standard plot was in the order of 100-700 and 80-560µg/ml for LRT and ALV, respectively. The molar absorptivity, sandells sensitivity, LOD, LOQ and other validation parameters have been assessed extensively and all the parameters seem to comply with the acceptance criteria. The proposed methods were proved to be more accurate, simple, precise and rapid by statistical validation, recovery studies and could be appropriate to employ in regular laboratory analysis.

Effect of loratadine on the dissolution and bioavailability of gliclazide from its hydroxypropyl-β-cyclodextrin complex

Gliclazide (GZD) is a hypoglycemic agent that has slow dissolution rate and variable bioavailability. Inclusion complex of GZD with hydroxypropyl-β-cyclodextrin (HPβCD) was prepared with the molar ratio 1:2 by solvent evaporation method. The complex was characterized using Fourier transform infra-red spectroscopy and differential scanning calorimetry. Solubility and in vitro dissolution studies were performed at acidic and neutral pH values. Furthermore, the competitive interactions of the antihistamine loratadine (LOR) on the binding of GZD to HPβCD were studied by performing solubility and in vitro dissolution studies of GZD-HPβCD complex in presence and absence of the competing drug at pH values 4.5 and 6.8. GZD-HPβCD complex was found to enhance the dissolution of the drug in all pH values studied. The presence of LOR with GZD-HPβCD complex led to some pH dependent changes in the dissolution of the complex which supported the results obtained from the solubility studies. Using blood glucose level as a pharmacodynamic marker that reflects the bioavailability of GZD, in vivo studies have shown that GZD when given as its HPβCD complex together with LOR exhibits about 25 % lower bioavailability (effect) compared to GZD alone. In an attempt to explain the in vivo and dissolution studies, higher order complexes (aggregates) involving LOR, GZD and HPβCD were proposed. The formation of such larger complexes was supported by stoichiometric and diffusion studies.