Design, Synthesis, Evaluation of Antimicrobial Activity and Docking Studies of New Thiazole-based Chalcones.

BACKGROUND: Thiazole derivates as well as chalcones, are very important scaffold for medicinal chemistry. Literature survey revealed that they possess wide spectrum of biological activities among which are anti-inflammatory and antimicrobial. OBJECTIVES: The current studies describe the synthesis and evaluation of antimicrobial activity of twenty eight novel thiazole-based chalcones. METHODS: The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method. RESULTS: All compounds have shown antibacterial properties better than that of ampicillin and in many cases better than streptomycin. As far as the antifungal activity is concerned, all compounds possess much higher activity than reference drugs bifonazole and ketoconazole. The most sensitive bacterial species was B. cereus (MIC 6.5-28.4 µmol × 10-2/mL and MBC 14.2-105.0 µmol × 10-2/mL) while the most resistant ones were L. monocytogenes (MIC 21.4-113.6 µmol × 10-2/mL) and E. coli (MIC 10.7- 113.6 µmol × 10-2/mL) and MBC at 42.7-358.6 µmol × 10-2/mL and 21.4-247.2 µmol × 10-2/mL, respectively. All the compounds exhibited antibacterial activity against the three resistant strains, MRSA, P. aeruginosa and E.coli. with MIC and MBC in the range of 0.65-11.00 µmol/mL × 10-2 and 1.30-16.50 µmol/mL × 10-2. Docking studies were performed. CONCLUSION: Twenty-eight novel thiazole-based chalcones were designed, synthesized and evaluated for antimicrobial activity. The results showed that these derivatives could be lead compounds in search of new potent antimicrobial agents. Docking studies indicated that DNA gyrase, GyrB and MurA inhibition may explain the antibacterial activity.

Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics.

Biotin is very important for the survival of Mycobacterium tuberculosis. 7,8-Diamino pelargonic acid aminotransaminase (DAPA) is a transaminase enzyme involved in the biosynthesis of biotin. The benzothiazole title compounds were investigated for their in vitro anti-tubercular activity against two tubercular strains: H37Rv (ATCC 25,177) and MDR-MTB (multidrug-resistant M. tuberculosis, resistant to isoniazid, rifampicin, and ethambutol) by an agar incorporation method. The possible binding mode and predicted affinity were computed using a molecular docking study. Among the synthesized compounds in the series, the title compound {2-(benzo[d]thiazol-2-yl-methoxy)-5-fluorophenyl}-(4-chlorophenyl)-methanone was found to exhibit significant activity with minimum inhibitory concentrations of 1 µg/mL and 2 µg/mL against H37Rv and MDR-MTB, respectively; this compound showed the highest binding affinity (-24.75 kcal/mol) as well.

Synthesis and Structural Elucidation of Novel Benzothiazole Derivatives as Anti-tubercular Agents: In-silico Screening for Possible Target Identification.

BACKGROUND: Benzothiazole derivatives are known for anti-TB properties. Based on the known anti-TB benzothiazole pharmacophore, in the present study, we described the synthesis, structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives (BNTZ 1-7 and BNTZ 8-13). OBJECTIVE: The study aims to carry out the development of benzothiazole based anti-TB compounds. METHODS: Title compounds are synthesized by microwave method and purified by column chromatography. Characterization of the compounds is achieved by FT-IR, NMR (1H and 13C), LCMS and elemental analysis. Screening of test compounds for anti-TB activity is achieved by Resazurin Microplate Assay (REMA) Plate method. RESULTS: It was noted that the BNTZ compound with an isoquinoline nucleus (BNTZ 9) exhibited remarkable anti-tubercular activity at 8 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of Mycobacterium tuberculosis. On the other hand, the BNTZ compound with a naphthalene nucleus (BNTZ 2) revealed anti-tubercular activity at 6 µg/mL and 11 µg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis strains of M. tuberculosis, respectively. One of the selected BNTZ derivatives BNTZ 13 was used for single crystal X-ray studies. CONCLUSION: To identify the appropriate target for potent BNTZ compounds from the series, molecular modeling studies revealed the multiple strong binding of several BNTZs with mycobacterium lysine-ɛ-aminotransferase and decaprenyl-phosphoryl-ß-D-ribose 2'-oxidase. The interaction is derived by forming favorable hydrogen bonds and stacking interactions. This new class of BNTZ compounds gave promising anti-tubercular actions in the low micromolar range, and can be further optimized on a structural basis to develop promising, novel, BNTZ pharmacophore-based anti-tubercular drugs.

New Benzothiazole-based Thiazolidinones as Potent Antimicrobial Agents. Design, synthesis and Biological Evaluation.

BACKGROUND: Thiazole and benzothiazole derivatives, as well as thiazolidinones are very important scaffolds in medicinal chemistry. Literature has revealed that they possess a wide spectrum of biological activities including antimicrobial activity. OBJECTIVE: The goal of this paper is the designing of new benzothiazole based thiazolidinones and the evaluation of their biological activities. METHODS: The designed compounds were synthesized using classical organic synthesis methods. The antimicrobial activity was evaluated using the method of microdilution. RESULTS: The twelve newly synthesized compounds showed antimicrobial properties. All compounds appeared to be more active than ampicillin in most studied strains and in some cases, more active than streptomycin. Antifungal activity, in most cases was also better than the reference drugs ketoconazole and bifonazole. The prediction of cytotoxicity revealed that the synthesized compounds were not toxic (LD50 350-1000 mg/kg of body weight). Docking studies on the antibacterial activity confirmed the biological results. CONCLUSION: The twelve new compounds were synthesized and studied for their antimicrobial activity. The compounds appeared to be promising antimicrobial agents and could be the lead compounds for new, more potent drugs. According to the docking prediction, the compounds could be MurB inhibitors.

Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis.

The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, (1)H, and (13)C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 µg/mL, respectively.

Development and evaluation of buccal films impregnated with selegiline-loaded nanospheres.

Poor peroral therapeutic efficiency of selegiline is primarily due to the extensive hepatic metabolism and hence the need for an alternative route of administration. The present study is based on evaluation of a buccal film which is impregnated with selegiline nanospheres to enhance the systemic bioavailability. Selegiline-loaded nanospheres prepared using poly(lactide-co-glycolide) was embedded into buccal films (F1-F4) with varying polymer composition [hydroxypropyl methylcellulose and eudragit]. The developed films were evaluated for their physicomechanical properties, hydration, mucoadhesive strength, in vitro drug release and ex vivo permeation in order to identify the ideal system suitable for further development. In vivo studies were carried out on rabbits to assess the comparative pharmacokinetics profile of the selected buccal film with oral solution. Preliminary studies indicated that the prepared films exhibited excellent physical properties, adequate mucoadhesive strength and moderate hydration. In vitro drug release data of the buccal films (F1, F2 and F3) showed distinct profiles. Permeation studies indicated higher steady-state flux from film F3 (p < 0.0001) when compared to film F2. In-vivo results of film (F3) demonstrated significant increase in absorption (p < 0.0001), Cmax (∼1.6-fold), Tmax, AUC0-α (∼3-fold, p < 0.0001) and improved bioavailability, when compared to control. This study concludes that the buccal delivery of selegiline using the developed buccal film (F3) would be a promising alternative approach for the treatment of Parkinson's disease.

Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir.

Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-α (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir.

Design, synthesis, and computational studies on dihydropyrimidine scaffolds as potential lipoxygenase inhibitors and cancer chemopreventive agents.

Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of cancer when compared to normal cells. The development of novel lipoxygenase inhibitors can have a major role in cancer therapy. A series of substituted 1,4-dihydropyrimidine analogues were synthesized and characterized by (1)H-NMR, (13)C-NMR, and HRMS. Molecular docking against lipoxygenase enzyme (protein data bank code =3V99) was done using Molecular Operating Environment 2013.08 and Leadit 2.1.2 softwares and showed high affinities. The synthesized compounds were tested for their lipoxygenase inhibitory activity and showed inhibition ranging from 59.37%±0.66% to 81.19%±0.94%. The activity was explained by a molecular docking study. The title compounds were also tested for cytotoxic activity against two human cancer cell lines Michigan Cancer Foundation-7 and human melanoma cells and a normal peripheral blood mononuclear cell line.

Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion.

Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer-Peppas kinetic model with an R (2) of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).

Noninvasive sampling of gabapentin by reverse iontophoresis.

PURPOSE: Transdermal reverse iontophoresis offers a noninvasive tool for clinical and therapeutic monitoring of drugs and endogenous molecules. This study investigated the viability of reverse iontophoresis as an alternative technique to blood sampling for the monitoring of gabapentin. METHODS: Ex vivo studies assessed the influence of polarity, applied current (0.064-0.32 mA) and subdermal concentration (0.5-20 µg/mL) on the recovery of gabapentin. These experiments were carried out in vertical Franz diffusion cell for a period of 3 h using rat skin. In vivo experiments examined the versatility of this method to extract gabapentin from the subdermal region following intravenous administration of gabapentin (30 mg/kg) in rat model. RESULTS: Preliminary studies demonstrate that greater amount of gabapentin was extracted in the cathodal chamber due to the contribution of electroosmosis. Increasing the current intensity significantly enhances the extraction flux (P < 0.005) and shown linear relation (r(2) = 0.84) between the applied electrical dose (mA*h) and the amount of gabapentin recovered (µg). Indeed, transdermal iontophoresis of gabapentin was found to be concentration dependent in the range studied (0.5-20 µg/mL), which includes clinically relevant level. Further, a linear relationship was established between the iontophoretically recovered gabapentin 3 h flux values and the subdermal concentrations studied. The linear correlation with good regression value (r(2) = 0.92) observed in the in vivo studies infers that the drug in the plasma is proportionally extracted through the skin and potentially represents the subdermal drug concentrations. CONCLUSIONS: Given the promising results, this study concludes that the transdermal reverse iontophoresis technique could be a promising alternative for the noninvasive monitoring of gabapentin.

Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-ß-cyclodextrin.

The therapeutic potential of acyclovir is limited by the low oral bioavailability owing to its limited aqueous solubility and low permeability. The present study was a systematic investigation on the development and evaluation of inclusion complex using hydroxypropyl-ß-cyclodextrin for the enhancement of oral bioavailability of acyclovir. The inclusion complex of acyclovir was prepared by kneading method using drug: hydroxypropyl-ß-cyclodextrin (1:1 mole). The prepared inclusion complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, NMR spectroscopy and evaluated in vitro by dissolution studies. In vivo bioavailability of acyclovir was compared for inclusion complex and physical mixture in rat model. Phase solubility studies indicate the formation of acyclovir-hydroxypropyl-ß-cyclodextrin complex with higher stability constant and linear enhancement in drug solubility with increase in hydroxypropyl-ß-cyclodextrin concentration. Characterization of the prepared formulation confirms the formation of acyclovir-hydroxypropyl-ß-cyclodextrin inclusion complex. Dissolution profile of inclusion complex demonstrated rapid and complete release of acyclovir in 30 min with greater dissolution efficiency (90.05 ± 2.94%). In vivo pharmacokinetic data signify increased rate and extent of acyclovir absorption (relative bioavailability ∼160%; p < 0.0001) from inclusion complex, compared to physical mixture. Given the promising results in the in vivo studies, it can be concluded that the inclusion complex of acyclovir could be an effective and promising approach for successful oral therapy of acyclovir in the treatment of herpes viruses.

Pharmacokinetics and tissue distribution of spray-dried carboplatin microspheres: lung targeting via intravenous route.

For cancer therapy, microspheres can be used to increase effectiveness while decreasing side effects of treatments. We prepared gelatin microspheres containing carboplatin (GCPtM) for treating lung cancer. We prepared gelatin microspheres of carboplatin (GCPtM) for use in treating lung cancer. Microspheres were prepared using a Buchi B-90 nano spray-drier. Surface morphology was found to be shriveled to nearly spherical, with an average size of 14.7 µm. Drug loading and percentage yield were found to be 72 ± 0.4 and 88 ± 0.2 %, respectively. In vitro release studies indicated that diffusion followed the Peppas model, with 99.3 % of total carboplatin released from GCPtM after 12 h, while for the pure drug this value was 92.4 % in 0.5 h. Liquification was observed during stability studies at 37 °C with an relative humidity of 75 %. Plasma concentration profile was described using a two-compartment model after intravenous injection of GCPtM. Carboplatin containing microspheres distributed in the lung, spleen, liver, and blood were found to be primarily distributed in the lungs. We used a powder technology (spray-dryer) method in this study to significantly reduce the overall production time and desired particle size, without using organic solvents; additionally, this method is economically feasible. Thus, microsphere may be an effective method for successfully delivering carboplatin to the lungs.

Skin uptake and clearance of ciclopirox following topical application.

The assessment of skin uptake and clearance are important to determine the efficiency and systemic safety of dermatological formulations. The objective of this study was to assess the skin uptake, clearance and possible systemic delivery of ciclopirox following topical application in Wistar rats. In vitro studies (3 h) were carried out in excised pig skin to assess the permeation and retention capacity of ciclopirox in skin layers using gel formulations (1% and 2% w/v). In vivo dermatopharmacokinetics (DPK) parameters were determined by measuring the drug levels in the skin as a function of time post application (0.5, 1, 1.5 and 2 h) and post removal (3, 4, 6 and 8 h) of the formulation in Wistar rats. The plasma drug concentrations were also determined in the same animals. In vitro data indicate the low permeability and high retention of ciclopirox in the stratum corneum. The DPK data observed indicate a higher Cmax value (175.43 ± 25.62 µg/cm2) and AUC (632.14 ± 102.26 µg.h/cm2) with the 2% (w/v) gel formulation. Further, the skin elimination of ciclopirox follows first order kinetics with a short half-life (t1/2 ~2 h). The fraction of drug reaching the systemic circulation was found to be significantly low (~0.15% of the applied dose). A relation between the drug concentration in the skin layers and the plasma was observed with a short lag period. The topical availability of ciclopirox was found to be relatively low and endured rapid clearance with minimal systemic uptake.

Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization.

Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology--the Büchi Nano Spray Dryer B-90 - and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm(3). In vitro drug release of formulations was best fitted by first-order and Peppas models with R (2) of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25 °C ± 2 °C and 60% ± 5% relative humidity.

Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract.

OBJECTIVE: To clarify the modulatory effects of daily consumption of pomegranate extract (PE), olive oil (OO) and Nagilla sativa oil (NSO) on antioxidant activity, sperm quality and pituitary-testicular axis of adult male wistar rats. METHODS: Thirty-two adult male Wistar rats were divided into four equal groups, eight rats each. Using rat gastric tubes, 1.0 mL distilled water, 1.0 mL PE, 0.4 mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first, second, third and fourth groups, respectively. Reproductive organs, body weight, sperm criteria, testosterone, FSH, LH, inhibin-B, lipid peroxidation, and antioxidant enzyme activities were investigated. At the end of the study protocol, analyses occurred at the same time. Data were analysed by ANOVA test and P<0.05 was considered to be a significant value. RESULTS: In all studied groups, malondialdehyde level was significantly decreased accompanied with an increases in glutathione peroxidase and glutathione. Rats treated with PE showed an increase in catalase activities accompanied with an increase in sperm concentration which was also observed in NSO group. In PE treated group, sperm motility was also increased accompanied with decreased abnormal sperm rate. NSO, OO and PE treated groups shows an insignificant effect on testosterone, inhibin-B, FSH and LH in comparison with control group. CONCLUSIONS: These results show that administration of PE, NSO and OO could modify sperm characteristics and antioxidant activity of adult male wistar rats.

A comprehensive study to evaluate the effect of constant low voltage iontophoresis on transungual delivery.

Treatment of nail diseases by topical drug delivery continues to draw much attention in the recent days. This study aims to systematically investigate the effect of constant voltage iontophoresis in the transungual drug delivery, using ciclopirox as a model drug. Preliminary permeation studies were carried out by applying constant voltage (6 V for 24 h) using a gel formulation across the human nail plate in a Franz diffusion cell. Different protocols have been studied to authenticate the potential of the proposed technique. Antifungal studies were carried out to assess the pharmacodynamic effect of drug depot formed in the nail plate. Initial studies revealed that application of constant voltage iontophoresis enhanced the permeation by an order of magnitude (p = 0.019) and delivered significant amount of drug into the deeper nail layers. Noticeably higher permeation was observed during the active phase in on-off studies. Excellent correlation was observed in permeation (r(2) = 0.98) and drug load (r(2) = 0.97) with the increase in applied voltage (3-12 V), indicating that the current technique is predictable. The data observed suggest that any further increase in voltage could eventually lead to increase in the permeation and drug load, as the saturation level is very distant. Furthermore, the enhancement in permeation with the applied voltage (3-12 V) was found to be 6-20 folds, compared to the passive process. Results of step up and step down studies substantiated the viability of the current technique. Zone of inhibition measured during the antifungal studies demonstrated that the drug molecules loaded into the nail plate by low voltage iontophoresis is active and releases over an extended period of time (~32 days). Given the excellent results, the current technique could be used as an effective approach for the delivery of antimycotics, which would localize the drug at the infection site and potentially offer higher patient compliance.

Design and formulation of mucoadhesive microspheres of sitagliptin.

Mucoadhesive microspheres of sitagliptin (SITCM), a new anti-diabetic drug was prepared with carbopol 934 P using Buchi B-90 nano spray drier and optimized to analyse the key effects and relations of three factors on formulation of SITCM were studied. The appearance of the microspheres was found to be shriveled to nearly spherical, with a narrow size of 2-8 µm. The drug loading and percentage yield was found to be 73 ± 0.2% and 92 ± 0.3%, respectively. In vitro release indicated Korsmeyer-Peppas pattern mucoadhesion of SITCM-8 was found to be 7.8 ± 0.3 h. In vivo studies in rats suggest that the sitagliptin was retained in the gastrointestinal tract for an extended period of time (∼12 h) and control group was reduced significantly (∼4 h). This study concludes that the mucoadhesive microsphere could be one of the most appropriate drug delivery approaches for the successful delivery of sitagliptin.

In vitro techniques to evaluate buccal films.

Extensive research on transmucosal drug delivery in the past few decades has resulted in the clinical application of several drug molecules through the buccal route. Interestingly, most of the new chemical moieties under clinical trials are being screened for their potential to deliver through the buccal cavity. In this context, buccal film offers several advantages including convenient dosing and better patient compliance. However, the greatest challenge is to develop a high quality buccal film which also necessitates constant evaluation and understanding the performance of the dosage form, the critical steps to achieve a successful product development. Despite the intense focus on buccal film based drug delivery system, there are no official standardized methods for its evaluation. Significant efforts have been made to demonstrate and improve the efficacy, potency and safety of buccal film using in vitro, ex vivo and in vivo assessments. Besides the physical properties of the film, several other parameters such as residence time, mucoadhesion, drug release, in vitro and in vivo buccal permeation profiles and absorption kinetics of the drug are examined while characterizing the prepared buccal films. However, various research groups have employed different methods and experimental conditions to evaluate the formulation, which has limited the comparison of data between the research groups. This review provides an overview about the various parameters that are considered and assessed as a part of formulation development to ensure quality product with desired characteristics.

Basic considerations in the dermatokinetics of topical formulations

Assessing the bioavailability of drug molecules at the site of action provides better insight into the efficiency of a dosage form. However, determining drug concentration in the skin layers following topical application of dermatological formulations is a great challenge. The protocols followed in oral formulations could not be applied for topical dosage forms. The regulatory agencies are considering several possible approaches such as tape stripping, microdialysis etc. On the other hand, the skin bioavailability assessment of xenobiotics is equally important for topical formulations in order to evaluate the toxicity. It is always possible that drug molecules applied on the skin surface may transport thorough the skin and reaches systemic circulation. Thus the real time measurement of molecules in the skin layer has become obligatory. In the last two decades, quite a few investigations have been carried out to assess the skin bioavailability and toxicity of topical/dermatological products. This review provides current understanding on the basics of dermatokinetics, drug depot formation, skin metabolism and clearance of drug molecules from the skin layers following application of topical formulations.

A avaliação da biodisponibilidade de moléculas de fármacos no sítio de ação oferece melhor compreensão sobre a eficiência da forma de dosagem. Entretanto, a determinação da concentração de fármaco nas camadas da pele em seguida à aplicação tópica de formulações dermatológicas é um grande desafio. Os protocolos seguidos para as formulações orais não podem ser aplicados para as formulações tópicas. As agências regulatórias consideram várias abordagens possíveis, tape stripping, microdiálise etc. Por outro lado, a avaliação da biodisponibilidade de xenobióticos na pele é igualmente importante para as formulações tópicas para se avaliar a toxicidade. É sempre possível que as moléculas de fármaco aplicadas na superfície da pele sejam transportadas através da pele e alcancem a circulação sistêmica. Assim, a medida em tempo real de moléculas na camada da pele tem se tornado obrigatória. Nas últimas duas décadas, realizaram-se poucas pesquisas para avaliar a biodisponibilidade da pele e a toxicidade de produtos tópicos/dermatológicos. Esta revisão fornece a compreensão atual com base na dermatocinética, formação de fármaco de depósito, metabolismo da pele e o clearance das moléculas de fármaco das camadas da pele em seguida à aplicação de formulações tópicas.

Análisis y evaluación de prescripciones en Al-Ahsa, Arabia Saudi / Analysis and evaluation of prescriptions in Al-Ahsa (Saudi Arabia)

Objetivo: Los fallos de medicación, generalmente definidos como cualquier error en el asesoramiento, distribución o manejo de un tratamiento, sin importar si dichos errores conllevan sanciones o no, son la causa más inevitable de mal tratamiento en el paciente. Las tasas de errores de medicación estudiadas son muy variables, como resultado de la alta variedad de definiciones y métodos de estudio utilizados. Miles de personas mueren en el mundo cada año debido a errores de prescripción lo que supone un gasto anual de miles de millones de dólares. El presente estudio se llevó a cabo en el departamento de Farmacia Práctica, Facultad de Farmacia Clínica, Universidad de King Faisal, Al-Ahsa, Arabia Saudí del 1 de Octubre de 2010 al 31 de Diciembre de 2011 con el objetivo de investigar errores de prescripción. Material y método: Las prescripciones fueron recogidas de diferentes hospitales de la región este de Arabia Saudí y fueron analizadas en el departamento de Farmacia Práctica, Facultad de Farmacia Clínica. La información de las prescripciones fue analizada estadísticamente. Resultados: Se procesaron un total de 500 prescripciones. Tras la evaluación se detectaron errores fatales como edad (4,6%), peso (98,8%), diagnóstico (30%), o dosificación (14,6%), que no fueron notificados. Se detectaron errores adicionales e inconsistencias en las prescripciones estudiadas. Conclusión: Es necesario una revisión en profundidad de los sistemas gubernamentales para el control de los errores de prescripción en Al-Ahsa, Arabia Saudí(AU)

Aims: Medication faults, broadly defined as any error in the advising, distributing, or management of a treatment, nevertheless whether such mistakes lead to confrontational penalties or not, are the single most inevitable cause of patient maltreatment. Incidences of medication error rates vary widely, as a result of the variety of altered study methods and descriptions used. Several thousand individuals are dying in the world because of the prescription errors every year, at the same time these errors cost billions of dollars annually. This study was conducted in the department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia from 1st October 2010 to 31st December 2011, to investigate the prescriptions regarding errors. Materials and Methods: The prescriptions were collected from different hospitals of Eastern region of Saudi Arabia and analyzed in the department of Pharmacy Practice College of Clinical Pharmacy Al-Ahsa. The information in the prescriptions was evaluated statistically. Results: A total of 500 prescriptions were processed. In evaluation it was found that out of 500 prescriptions were having fatal errors like age (4.6%), weight (98.8%), Diagnosis (30%), Dosage (14.6%), were not declared. Along with that a number of errors and inconsistencies were noticed in the prescriptions studied. Conclusion: There is need of a comprehensive review of the government’s control system on prescription error in Al-Ahsa, Saudi Arabia(AU)