Roop Khar

New, simple, cost effective, accurate and reproducible UV-spectrophotometric methods were developed and validated for the estimation of moxifloxacin in bulk and pharmaceutical formulations. Moxifloxacin was estimated at 296 nm in 0.1N hydrochloric acid (pH 1.2) and at 289 nm in phosphate buffer (pH 7.4). Beer's law was obeyed in the concentration range of 1-12 microg ml(-1) (r2=0.9999) in hydrochloric acid and 1-14 microg ml(-1) (r2=0.9998) in the phosphate buffer medium. The apparent molar absorptivity and Sandell's sensitivity coefficient were found to be 4.63 x 10(4) l mol(-1) cm(-1) and 9.5 ng cm(-2)/0.001 A in hydrochloric acid; and 4.08 x 10(4) l mol(-1) cm(-1) and 10.8 ng cm(-2)/0.001 A in phosphate buffer media, respectively indicating the high sensitivity of the proposed methods. These methods were tested and validated for various parameters according to ICH guidelines. The detection and quantitation limits were found to be 0.0402, 0.1217 microg ml(-1) in hydrochloric acid and 0.0384, 0.1163 microg ml(-1) in phosphate buffer medium, respectively. The proposed methods were successfully applied for the determination of moxifloxacin in pharmaceutical formulations (tablets, i.v. infusions, eye drops and polymeric nanoparticles). The results demonstrated that the procedure is accurate, precise and reproducible (relative standard deviation <2%), while being simple, cheap and less time consuming and hence can be suitably applied for the estimation of moxifloxacin in different dosage forms and dissolution studies.

Simple, accurate, reproducible, selective, sensitive and cost effective UV-spectrophotometric methods were developed and validated for the estimation of trigonelline in bulk and pharmaceutical formulations. Trigonelline was estimated at 265 nm in deionised water and at 264 nm in phosphate buffer (pH 4.5). Beer's law was obeyed in the concentration ranges of 1-20microg mL(-1) (r2=0.9999) in deionised water and 1-24 microg mL(-1) (r2=0.9999) in the phosphate buffer medium. The apparent molar absorptivity and Sandell's sensitivity coefficient were found to be 4.04 x 10(3)L mol(-1)cm(-1) and 0.0422 microg cm(-2)/0.001A in deionised water; and 3.05 x 10(3)L mol(-1)cm(-1) and 0.0567 microg cm(-2)/0.001A in phosphate buffer media, respectively. These methods were tested and validated for various parameters according to ICH guidelines. The detection and quantitation limits were found to be 0.12 and 0.37 microg mL(-1) in deionised water and 0.13 and 0.40 microg mL(-1) in phosphate buffer medium, respectively. The proposed methods were successfully applied for the determination of trigonelline in pharmaceutical formulations (vaginal tablets and bioadhesive vaginal gels). The results demonstrated that the procedure is accurate, precise, specific and reproducible (percent relative standard deviation <2%), while being simple and less time consuming and hence can be suitably applied for the estimation of trigonelline in different dosage forms and dissolution studies.

A rapid, sensitive and specific high-performance thin-layer chromatographic (HPTLC) method was developed and validated for determination of minocycline in human plasma, saliva, and gingival fluid samples. Densitometric analysis of minocycline was carried out at 345 nm after single step extraction with methanol. The method uses TLC aluminium plates pre-coated with silica gel 60F-254 as a stationary phase and methanol-acetonitrile-isopropyl alcohol-water (5:4:0.5:0.5, v/v/v/v) as mobile phase. In all the three matrices, the calibration curve was linear (r(2) >/= 0.9958) in the tested range of 100 - 1200 ng spot(-1) with a limit of quantification of 15.4 ng spot(-1). Drug recovery from plasma, saliva and gingival fluid averaged 97.7%. Intra- and inter-day accuracies, determined at three different concentrations, were 95.08 to 100.6% and the corresponding precision (% CV) values were < 4.61%. In all the three matrices, rapid degradation of drug occurred and the half-life of drug ranged from 9.9 to 16.1 h at 4 degrees C and from 6.3 to 11.5 h at 20 degrees C. Frozen at -20 degrees C, this drug was stable for at least 2 months and can tolerate two freeze-thaw cycles without losses higher than 10%. The method's ability to quantify minocycline with precision, accuracy and sensitivity makes it useful in pharmacokinetic studies.

CD44 or hyaluronan receptor is a transmembrane receptor associated with aggressive tumour growth, proliferation, and metastasis. In normal physiology, this receptor has a crucial role in cell adhesion, inflammation, and repair processes. However, many tumour cells over-express this receptor and abuse it to become progressive and perpetual units. The article comments from common functioning of the CD44 receptor, to its diabolic multi-dimensional effects in promotion of malignant cells. It also illuminates the relations of CD44 endorsed processes with other biomolecular events in cancer progression. In an end, the review focuses comprehensively at ongoing researches to exploit the CD44 over-expression as a probable target in treatment, management, and diagnosis of malignancy.

A new, simple, sensitive and specific reversed-phase high performance liquid chromatographic (HPLC) method using ultraviolet detection was developed and validated for the analysis of CPT-11 (λmax=254nm, 365nm) and its major active metabolite, SN-38 (λmax=380nm) in rat plasma and bile. The sample pre-treatment from plasma involved a single protein precipitation step with cold acetonitrile. In case of bile, liquid–liquid extraction with

... K. Khar a , Md. Faiyazuddin a , Farhan J. Ahmad a , Zeenat Iqbal a & Manu Jaggi b ... View all references , 15 15. Ali , J. ; Ali , N. ; Sultana , Y. ; Baboota , S. ; Faiyaz , S. Development and Validation of a Stability-Indicating HPTLC Method for Analysis of Antitubercular Drugs . ...

Chemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter

Tea tree oil, a popular antimicrobial agent is recommended for the treatment of acne vulgaris, a disease of the pilosebaceous unit. Tea tree oil formulations (colloidal bed, microemulsion, multiple emulsion, and liposomal dispersion containing 5% w/w tea tree oil) were applied to bovine udder skin. The follicular uptake of tea tree oil upon application was determined by a cyanoacrylate method. Tea tree oil was determined by quantifying terpinen-4-ol content using high-performance thin layer chromatography. The accumulation of tea tree oil in the follicular casts was 0.43 +/- 0.01, 0.41 +/- 0.009, 0.21 +/- 0.006, and 0.16 +/- 0.005 percentage by weight (milligram oil/gram of sebum plug) for microemulsion, liposomal dispersion, multiple emulsion, and colloidal bed, respectively. This is the first study of its kind to quantify tea tree oil concentration in the follicles.

In the present study, mucoadhesive alginate microspheres of acyclovir were prepared to prolong the gastric residence time using a simple emulsification phase separation technique. The particle size of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope and mastersizer. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (70.60 ± 2.44 µm). The results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and decreased with increase in stirring speed. The entrapment efficiency was found to be in the range of 51.42-80.46%. The concentration of the calcium chloride (% w/v) of 10% and drug-polymer ratio of 1:4 resulted in an increase in the entrapment efficiency and the extent of drug release. The optimized alginate microspheres were found to possess good mucoadhesion (66.42 ± 1.01%). The best fit model with the highest regression coefficient values (R²) was predicted by Peppas model (0.9813). In Gamma scintigraphy analysis, the section of GIT was critically analyzed and much differentiation was present at each time point after oral administration, which revealed that the optimized formulation demonstrated gastroretention in vivo for more than 4 h, which revealed that optimized formulation could be a good choice for gastroretentive systems.

A simple, sensitive and selective ultra performance liquid chromatographic (UPLC) method with quadrapole-time of flight-mass spectrometric (Q-TOF-MS/MS) detection was developed for the determination of moxifloxacin (moxi) in rabbit aqueous humor. After a simple protein-precipitation by acetonitrile, the post-treatment samples were separated on a UPLC Bridged Ethyl Hybrid (BEH) C-18 column with 0.1% formic acid in water as a mobile phase

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.

The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

Peroral administration of drugs, although most preferred by both clinicians and patients has several disadvantages such as hepatic first pass metabolism and enzymatic degradation within the GI tract, that prohibit oral administration of certain classes of drugs especially peptides and proteins. Consequently, other absorptive mucosae are considered as potential sites for administration of these drugs. Among the various transmucosal routes studied the buccal mucosa offers several advantages for controlled drug delivery for extended period of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract is avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form, design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation. Buccal drug delivery is thus a promising area for continued research with the aim of systemic and local delivery of orally inefficient drugs as well as feasible and attractive alternative for non-invasive delivery of potent protein and peptide drug molecules. Extensive review pertaining specifically to the patents relating to buccal drug delivery is currently available. However, many patents e.g. US patents 6, 585,997; US20030059376A1 etc. have been mentioned in few articles. It is the objective of this article to extensively review buccal drug delivery by discussing the recent patents available. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systems.

Safranal is an effective anticonvulsant shown to act as an agonist at GABA(A) receptors. Nose to brain delivery via nanoparticle formulation might improve its brain delivery. A selective and sensitive analytical method is required for evaluation of safranal-based novel drug delivery systems. To develop and validate a high-performance thin-layer chromatographic (HPTLC) method for the quantitative analysis of safranal as bulk, in saffron extract and in developed safranal-loaded nanoparticle formulation. Chromatographic separation was achieved on silica gel pre-coated TLC aluminium plates 60F-254, using n-hexane:ethyl acetate (9 : 1, v/v) as the mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 310 nm. The method was validated and applied to detect related impurities, to analyse safranal in saffron extract and to evaluate safranal-loaded nanoparticles. Compact spots of safranal were observed at R(f) value 0.51 +/- 0.02. The method was linear (r = 0.9991) between 0.5 and 5.0 ng/spot. The intra- and inter-day precisions were 1.08-2.17 and 1. 86-3.47%, respectively. The limit of detection was 50 ng/spot and the limit of quantification was 150 ng/spot. The method proved to be accurate (recovery 97.4-102.0%) and was selective for safranal. Evaluation of safranal-loaded nanoparticle formulation demonstrated drug loading of 23.0%, encapsulation efficiency of 42.0% and sustained drug release following biphasic pattern. The present method is useful for the quantitative and qualitative analysis of safranal and safranal-loaded nanoparticle formulation. It provides significant advantages in terms of greater specificity and rapid analysis.

The aim of the work was to develop, characterize, and carry out a clinical trial with nano-atropine sulfate (nano-AS) dry powder inhaler (DPI), because this route may offer several advantages over the conventional intramuscular route as an emergency treatment, including ease of administration and more rapid bioavailability. Different batches of nanoparticles of AS were produced using variants of nanoprecipitation method. The influence of the process parameters, such as the types and quantity of solvent and nonsolvent, the stirring speed, the solvent-to-nonsolvent volume ratio, and the drug concentration, was investigated. The methodology resulted in optimally sized particles. Bulk properties of the particles made by the chosen methodology were evaluated. A clinical trial was conducted in six healthy individuals using a single DPI capsule containing 6 mg nano-AS DPI in lactose. Early blood bioavailability and atropinization pattern confirmed its value as a potential replacement to parenteral atropine in field conditions. The formulation seems to have the advantage of early therapeutic drug concentration in blood due to absorption through the lungs as well as sustained action due to absorption from the gut of the remaining portion of the drug.

The present report describes a rapid and sensitive ultra high-pressure liquid chromatography (UHPLC) method with UV detection to quantify moxifloxacin in rabbit aqueous humor. After deproteinisation with acetonitrile, gradient separation of moxifloxacin was achieved on a Waters Acquity BEH C18 (50mmx2.1mm, 1.7microm) column at 50 degrees C. The mobile phase consisted of 0.1% trifluoroacetic acid in water and acetonitrile at a flow rate of 0.4ml/min. Detection of moxifloxacin was done at 296nm. Method was found to be selective, linear (r=0.9997), accurate (recovery, 97.30-99.99%) and precise (RSD, <or=1.72%) in the selected concentration range of 10-1000ng/ml. Detection and quantitation limit of moxifloxacin in aqueous humor were 0.75 and 2.5ng/ml, respectively. The aqueous humor levels of moxifloxacin after single topical instillation in three formulations, i.e. moxifloxacin solution (Moxi-SOL), anionic nanoparticles (Moxi-ANP) and cationic nanoparticles (Moxi-CNP) were investigated. A fourfold increase in the relative bioavailability was observed with the Moxi-CNP (AUC(0-->t), 3.14microg h/ml) compared with Moxi-SOL (AUC(0-->t), 0.79microg h/ml) and Moxi-ANP (AUC(0-->t), 0.72microg h/ml) formulation. The results indicate that the cationic nanoparticle increases ocular bioavailability of moxifloxacin and prolong its residence time in the eye.

The purpose of the current study was to investigate the feasibility of proniosomes as transdermal drug delivery system for losartan potassium. Different preparations of proniosomes were fabricated using different nonionic surfactants, such as Span 20, Span 40, Span 60, Span 80, Tween 20, Tween 40, and Tween 80. Different formulae were prepared and coded as PNG-1 (proniosomal gel-1) to PNG-7. The best in vitro skin permeation profile was obtained with proniosomal formulation PNG-2 in 24 h. The permeability parameters such as flux, permeability coefficient, and enhancement ratio were significant for PNG-2 compared with other formulations (P < 0.05). This optimized PNG-2 was fabricated in the form of transdermal patch using HPMC gel as a suitable base. Proniosomal transdermal therapeutic system (PNP-H) was found to be the optimized one as it gave better release of drug and better permeation in a steady-state manner over a desired period of time, that is, 24 h through rat skin. In vivo pharmacokinetic study of PNP-H showed a significant increase in bioavailability (1.93 times) compared with oral formulation of losartan potassium. The formulation appeared to be stable when stored at room temperature (30 +/- 2 degrees C) and at refrigeration temperature (4 +/- 2 degrees C) for 45 days.

Considering limitations of conventional insulin therapies, the present study characterizes usefulness of novel mucoadhesive multivesicular liposomes as a mucoadhesive sustained release carrier of insulin via nasal and ocular routes, thus attempts to develop non-invasive carrier system for the controlled release of bioactives. Multivesicular liposomes (MVLs) of 26-34 microm were prepared with a high protein loading (58-62%) and were coated with chitosan and carbopol. These mucoadhesive carriers were characterized by zeta potential studies, in vitro mucoadhesion test and insulin protective ability against nasal aminopeptidase. In vitro, mucoadhesive carriers released insulin for a period of 7-9 days compared to 24 h of conventional liposomes. After intranasal administration to STZ induced diabetic rats, the mucoadhesive MVLs (chitosan coated MVLs) effectively reduced plasma glucose level up to 2 days (35% reduction), compared to non-coated MVLs (32% at 12 h) and conventional liposomes (34% at 8 h). Although the differences are statistically insignificant, chitosan coated formulation has shown a better hypoglycemic profile as the effects were prolonged compared to carbopol coated formulation. When compared to ocular route, chitosan formulation after nasal administration has shown better therapeutic profile as the hypoglycemic effects were prolonged until 72 h. The effectiveness of this chitosan coated MVLs was further demonstrated by the significant quantities of ELISA detectable insulin levels after nasal (334.6 microIu/ml) and ocular (186.3 microIu/ml) administration. These results demonstrate that mucoadhesive carrier is a viable option for a sustained release transmucosal insulin carrier, and open an avenue to develop a non-invasive carrier platform for the controlled release of bioactives.

Ultraviolet (UV) radiation has been implicated in photoaging and various types of skin carcinomas. Although the human skin has evolved several defense mechanisms to survive the insults of actinic damage like keratinization, melanin pigmentation, etc., it is still subjected to the harmful effects of sunlight. In this study, the role of almond oil in reducing the degradative changes induced in skin upon exposure to UV radiation was investigated. Mice were divided in four groups of 20 animals. Group I was the control group. Group II was negative control, which received almond oil treatment alone. Group III was exposed to UV radiation only and Group IV received both UV treatment and almond oil treatment. Visible skin grading assessed the changes based on a rating scale, biochemical tests (glutathione estimation and lipid peroxidation), and histopathologic studies. Upon exposure of mice to UV radiation, it was found that pronounced visible skin changes were seen after 12 weeks of exposure. The results of the biochemical tests, glutathione estimation, and lipid peroxidation showed that almond oil reduced the effect of UV light-induced photoaging on the skin. Histopathologic studies also indicated a photoprotective effect of almond oil on the skin after UV exposure. It was concluded that topical almond oil is capable of preventing the structural damage caused by UV irradiation and it was also found useful in decelerating the photoaging process.