Publications

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    ABSTRACT: 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.
    Colloids and surfaces B: Biointerfaces 07/2014; 122C:423-431. · 4.28 Impact Factor
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    ABSTRACT: Abstract Availability of proper concentration of medicament on to the corneal surface is a challenging task. Many novel formulations, i.e. hydrogels, nanoparticles, ocuserts, etc. had been tested to improve ocular bioavailability, out of which our group found, in situ gel and polymeric nanoparticle are the most interesting approach to achieve ocular retention. We found that in situ gel stay only for 12 h and poly(lactic-co-glycolic acid (PLGA) nanoparticles are non mucoadhesive in nature so we try to combine both these formulations and termed it as "Nanoparticle laden in situ gel". Here we prepare nanoparticle laden in situ gel containing levofloxacin encapsulated PLGA nanoparticle, incorporated in chitosan in situ gel and evaluated its ocular retention by gamma scintigraphy in rabbits. The observations of acquired gamma camera images showed good retention over the entire precorneal area. From static and dynamic gamma scintigraphy evaluation, we can be interpret that developed nanoparticle laden in situ gel formulation cleared at a very slow rate and remained at corneal surface for longer duration than marketed formulation, in situ gel and nanosuspension alone.
    Drug Delivery 09/2013; 20(7):306-9. · 2.02 Impact Factor
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    ABSTRACT: The purpose of this work is intended to investigate the potential of self-nanoemulsifying (SNE) drug delivery system for enhanced oral bioavailability of etoposide by P-glycoprotein (P-gp) modulation. The components of SNE formulation were optimized by their solubilization and emulsification efficiency. The ternary phase diagrams provided nanoemulsion existence ranges and the corresponding formulations were developed and evaluated via thermodynamic and dispersibility tests. The successful formulations were characterized for various parameters including time required for self-emulsification, percentage transmittance, droplet size, surface morphology, zeta potential and in vitro release. The etoposide loaded SNE9 formulation showed 2.6- and 11-fold higher permeability coefficient in apical to basolateral direction across Caco-2 monolayers as compared to the Etosid and plain drug solution, respectively. The etoposide loaded SNE9 formulation showed a higher cytotoxicity at the highest tested concentration compared to the blank SNE9 formulation and the free etoposide. Furthermore, an in vivo pharmacokinetic study of etoposide in SNE9 formulation showed 3.2- and 7.9-fold increase in relative oral bioavailability compared with that of etoposide in Etosid and drug suspension, respectively. Thus, the developed SNE drug delivery system could be a valuable tool for the effective oral delivery of etoposide.
    Journal of Biomedical Nanotechnology 07/2013; 9(7):1216-29. · 7.58 Impact Factor
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    ABSTRACT: Abstract Collagen, a high molecular weight, hydrophilic and highly abundant protein is known to have anti-ageing, anti-wrinkle, anti-acne, anti-scar and wound healing properties. High molecular weight and hydrophilic nature hinder its effective topical delivery. So, the objective of present study was to develop effective topical nano-surfactant dispersion (NSD) for collagen delivery. NSD was prepared from sorbitan monostearate (Span60) and cholesterol using ethanol injection method followed by probe sonication. NSD was characterized for entrapment efficiency (%EE), size and size distribution (Z-avg and polydispersity index (PDI)), shape, zeta-potential (ζ), in vitro drug release, skin hydration and skin irritation test and histopathological examination. Optimized NSD (NSD3) had %EE, z-avg, PDI and ζ-potential of 77.56% ± 1.09%, 158.1 ± 2.31 nm, 0.211 and -17.2 ± 0.64 mV, respectively. In in vivo skin hydration test, NSD treatment showed nearly 2.5-fold and 3-fold increase in the thickness of stratum corneum (SC) as compared to the collagen gel treated and untreated skin, respectively. The mean scores of skin irritation test in two animal species, rats and rabbits, were found to be 1.42 ± 1.01 and 1.71 ± 0.29, respectively, indicating the non-irritant nature of collagen loaded NSD. Histopathology of the skin after application of developed NSD showed non-significant changes in skin anatomy indicating its safe nature.
    Pharmaceutical Development and Technology 05/2013; · 1.33 Impact Factor
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    ABSTRACT: H yperacute bacterial conjunctivitis is a severe, sight threatening ocular infection that warrants immediate ophthalmic work-up and management. Bacterial conjunctivitis requires treatment with antibiotics for 5-7 days that may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration, that is, 2-3 drops every 2-3 h. [1] This is because in ocular delivery, the physiological constraints imposed by the protective mechanisms of the eye lead to low absorption of drugs, resulting in short duration of the therapeutic effect. When a drug solution is dropped into the eye, the effective tear drainage and blinking action of the eye result in a 10-fold reduction in the drug concentration within 4-20 min. [1] The availability of medicament at corneal surface would be significantly improved if the precorneal residence time of drugs could be increased. Several new preparations such as inserts, [2] collagen shields, [3] and colloidal systems, such as liposomes, [4,5] nanoparticles, [6,7] and nanocapsules [8,9] have been developed for ophthalmic use, not only to prolong the ocular contact time of the vehicle but also to slow down drug elimination. [10] The use of nanotechnology-based drug delivery systems like microemulsions, nanosuspensions, nanoparticles, solid lipid nanoparticles, niosomes, dendrimers, and liposomes has led to the solution of various solubility-related problems of poorly soluble drugs, like dexamethasone, budesonide, ganciclovir, and so on. [11] However, these novel preparations have some disadvantages, such as poor compliance. Out of these novel formulations; in situ gel and nanoparticles have been established as the promising one. In our previous work, we found that these formulations have their own disadvantages. For example, in situ gel remains for 12-15 h, [12] whereas poly lactic co glycolic acid (PLGA) nanoparticles are nonmucoadhesive, so are drained out of eyes quickly. [13] In our present work, we try to combine both these formulation strategies as a nanoparticles suspended in liquid dosage form suitable to be administered by instillation into the eye which, upon exposure to physiological conditions, changes to the gel phase, thus increasing the precorneal residence time of the nanoparticles and enhancing ocular bioavailability. Our group has coined the term "nanoparticle laden in situ gel" for this formulation. [14] Nanoparticles laden in situ gel for sustained ocular drug delivery
    J Pharm Bioall Sci. 05/2013; 5(2):162-5.
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    ABSTRACT: Collagen, a high molecular weight, hydrophilic and highly abundant protein is known to have anti-ageing, anti-wrinkle, anti-acne, anti-scar and wound healing properties. High molecular weight and hydrophilic nature hinder its effective topical delivery. So, the objective of present study was to develop effective topical nano-surfactant dispersion (NSD) for collagen delivery. NSD was prepared from sorbitan monostearate (Span60) and cholesterol using ethanol injection method followed by probe sonication. NSD was characterized for entrapment efficiency (%EE), size and size distribution (Z-avg and polydispersity index (PDI)), shape, zeta-potential (ζ), in vitro drug release, skin hydration and skin irritation test and histopathological examination. Optimized NSD (NSD3) had %EE, z-avg, PDI and ζ-potential of 77.56% ± 1.09%, 158.1 ± 2.31 nm, 0.211 and -17.2 ± 0.64 mV, respectively. In in vivo skin hydration test, NSD treatment showed nearly 2.5-fold and 3-fold increase in the thickness of stratum corneum (SC) as compared to the collagen gel treated and untreated skin, respectively. The mean scores of skin irritation test in two animal species, rats and rabbits, were found to be 1.42 ± 1.01 and 1.71 ± 0.29, respectively, indicating the non-irritant nature of collagen loaded NSD. Histopathology of the skin after application of developed NSD showed non-significant changes in skin anatomy indicating its safe nature
    Pharmaceutical Development and Technology 05/2013; · 1.33 Impact Factor
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    ABSTRACT: Proper availability of drug on to corneal surface is a challenging task. However, due to ocular physiological barriers, conventional eye drops display poor ocular bioavailability of drugs (< 1%). To improve precorneal residence time and ocular penetration, earlier our group developed and evaluated in situ gel and nanoparticles for ocular delivery. In interest to evaluate the combined effect of in situ gel and nanoparticles on ocular retention, we combined them. We are the first to term this combination as "nanoparticle laden in situ gel", that is, poly lactic co glycolic acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery. The formulation was tested for various physicochemical properties. It showed gelation pH near pH 7.2. The observation of acquired gamma camera images showed good retention over the entire precorneal area for sparfloxacin nanoparticle laden in situ gel (SNG) as compared to marketed formulation. SNG formulation cleared at a very slow rate and remained at corneal surface for longer duration as no radioactivity was observed in systemic circulation. The developed formulation was found to be better in combination and can go up to the clinical evaluation and application.
    Journal of Pharmacy & Bioallied Sciences 04/2013; 5(2):162-5.
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    ABSTRACT: Acute lung injuries caused due to inhalation of toxic irritant gases such as ammonia, chlorine, hot smoke and burning plastic fumes predominantly affect the airways, causing tracheitis, bronchitis, and other inflammatory responses. The purpose was to develop and characterise nanoparticle based fluticasone propionate (FP) DPI formulation and assess its in vitro and in vivo pulmonary deposition using pharmacoscintigraphy. FP nanoparticles were prepared by nanoprecipitation method. Optimisation was carried out with the help of Box-Behnken statistical design. Nanoparticles were characterised with the help of SEM, FT-IR, DSC and XRD. Anderson cascade impaction showed that nano-FP exhibited significantly higher respirable fraction of 60.3 ± 2.41 as compared to 16.4 ± 0.66 for micronised form. Ventilation lung scintigraphy in human volunteers confirmed significant increase in drug delivery till alveolar region with nano-FP in comparison to micronised drug. Results indicate that the developed formulation may have a potential prophylactic/therapeutic role against toxic, irritant gas inhalation.
    Journal of Microencapsulation 02/2013; · 1.57 Impact Factor
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    ABSTRACT: The present investigation was aimed to establish a validated stability-indicating liquid chromatographic method for the estimation of etoposide (ETP) in bulk drug and self-nano emulsifying formulation. ETP was successfully separated from the degradation products formed under stress conditions on LiChrospher 100 C18 reverse-phase column (a 250 mm × 4.6 mm i.d., 5-μm particle size) using 55:45 (v/v) acetonitrile-phosphate buffer saline (pH 4.5) as the mobile phase, at a flow rate of 1.0 mL min(-1) and detection at 283 nm. The response was a linear function of analyte concentration (R(2) > 0.9997) over the concentration range of 0.05-50 μg mL(-1). The method was validated for precision, accuracy, robustness, sensitivity and specificity. The % recovery of ETP at three different levels (50%, 100% and 150%) ranged between 93.84% and 100.06% in optimized self-nano emulsifying formulation, Etosid® soft-gelatin capsule and Fytosid® injection. First-order degradation kinetics of ETP were observed under acidic and alkaline conditions. The method was also applied for the stability assessment of self-nano emulsifying formulation under accelerated conditions, the formulation was found to be stable at all storage conditions with the shelf-life of 2.37 years at 25 °C. The method holds promise for routine quality control of ETP in bulk, pharmaceutical formulations as well as in stability-indicating studies.
    Saudi Pharmaceutical Journal 01/2013; 21(1):103-11. · 0.95 Impact Factor
  • Roop Krishen Khar Kilam
    Journal of advanced pharmaceutical technology & research. 01/2013; 4(4):172.
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    ABSTRACT: A simple, rapid, precise and accurate isocratic reversed-phase high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of paclitaxel and ellagic acid in a combination nanoformulation. Separation was achieved using a 25 x 4.6 mm column, particle size 5 microm C18 reverse phase column (Luna), with a mobile phase consisting of methanol and 0.05% H3PO4, in gradient elution mode with a mobile phase flow rate of 1 mL/min, using UV visible detection at 230 nm. Sharp and well defined peaks were obtained at retention times of 13.75 min. and 11.6 min. for paclitaxel and ellagic acid, respectively. Regression analysis showed a good linear relationship (r2 = 0.996 +/- 0.0011) and (r2 = 0.993 +/- 0.0011) over wide ranges of 5-500 microg/ml and 1-500 microg/ml for paclitaxel and ellagic acid, respectively. LOD and LOQ of paclitaxel were 30 ng/ml and 100 ng/ml, respectively, while for ellagic acid LOD and LOQ were 300 ng/ml and 1 microg/ml, respectively. The accuracy of the method was determined by recovery studies using the standard addition method and was found to be in the range of 99.61-101.21% and 98.70-102.22% for paclitaxel and ellagic acid, respectively. The relative standard deviation (% RSD) for precision, repeatability and robustness was less than 2%. The ellagic acid content in fruits of Punica granatum and combination formulation with paclitaxel was analyzed and found to be 0.04% w/w and 0.0012%w/w, respectively. The proposed, developed and validated HPLC method for the simultaneous quantification of ellagic acid and paclitaxel can be used for the quality control and standardization of several crude drugs and different combination formulations, in which ellagic acid is present.
    Pharmazie 10/2012; 67(10):834-8. · 0.96 Impact Factor
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    ABSTRACT: 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.
    Journal of Drug Targeting 08/2012; 20(7):561-73. · 2.77 Impact Factor
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    ABSTRACT: Particle engineering is the prime focus to improve pulmonary drug targeting with the splendor of nanomedicines. In recent years, submicron particles have emerged as prettyful candidate for improved fludisation and deposition. For effective deposition, the particle size must be in the range of 0.5-5 µm. Inhalers design for the purpose of efficient delivery of powders to lungs is again a crucial task for pulmonary scientists. A huge number of DPI devices exist in the market, a significant number are awaiting FDA approval, some are under development and a large number have been patented or applied for patent. Even with superior design, the delivery competence is still deprived, mostly due to fluidization problems which cause poor aerosol generation and deposition. Because of the cohesive nature and poor flow characteristics, they are difficult to redisperse upon aerosolization with breath. These problems are illustrious in aerosol research, much of which is vastly pertinent to pulmonary therapeutics. A technical review is presented here of advances that have been utilized in production of submicron drug particles, their in vitro/in vivo evaluations, aerosol effects and pulmonary fate of inhaled submicron powders.
    Recent Patents on Inflammation & Allergy Drug Discovery 05/2012;
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    ABSTRACT: A rapid, simple, sensitive, selective, precise and robust thin-layer chromatography densitometric method for the determination of free sterols in leech was developed and validated on silica gel layer using carbon tetrachloride-methanol-formic acid (9.5:1.5:0.55, v/v/v). Spectrodensitometric scanning was carried using a Camag TLC scanner III at 366 nm after spraying 2% methanolic sulphuric acid, which gave compact spots for cholesterol (R(F) = 0.35 ± 0.02). The regression analysis data for calibration plot implied a good linear relationship (r(2) = 0.99958) between response and concentration over the range 100-600 ng per spot with respect to peak area. The limits of detection and quantification were found to be 13.8 ± 0.51 and 45.01 ± 1.29 ng per spot, respectively. Validation was in accordance to the International Conference on Harmonization guidelines. Cholesterol was subjected to forced stress conditions of oxidation, hydrolysis and heat. Degradation products resulting from the forced stress did not interfere with detection because the degradant peaks were well separated from the cholesterol peak. The densitometric method can be regarded as stability-indicating and can be used for quality control assay of cholesterol in leech extract.
    Journal of chromatographic science 05/2012; 50(8):673-9. · 0.79 Impact Factor
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    ABSTRACT: Terbutaline submicron particles (SμTBS) were prepared by nanoprecipitation technique followed by spray drying for deep lungs deposition. Inhalable SμTBS particles were 645.16 nm of diameter with 0.11μm of MMAD, suggested for better aerosol effects. Both submicron and micron-sized TBS particles were administered in rodents administered via major delivery routes, and their biological effects were compared by using UHPLC/ESI-q-TOF-MS method. TBS was found stable in all exposed conditions with 96.28-99.0% of recovery and <4.34% of accuracy (CV). An inhalation device was designed and validated to deliver medicines to lungs, which was found best at dose level of 25mg for 30 min of fluidization. Both submicron and micron particles were compared for in vivo lung deposition and a 1.67 fold increase in concentration was observed for SμTBS exposed by inhalation. Optimized DPI formulation contained lesser fraction of ultrafine particle (<500 nm) with the major fraction of submicron particles (>500 nm), advocated for better targeting to lungs. UHPLC/ESI-q-TOF-MS confirmed that designed submicron particles has been successfully delivered to the lungs. From tongue to lungs, the landing of pulmonary medicines can be improved by submicronization technology.
    International Journal of Pharmaceutics 05/2012; 434(1-2):59-69. · 3.99 Impact Factor
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    ABSTRACT: In this review we discuss insights into therapeutic stratagems that can selectively target the choroid, retinal cells and vitreoretinal space for the treatment of vision-threatening vascular degenerative disorders of the posterior eye. Despite the relative success of these novel drugs, new problems related to its delivery remain. Systems carrying drugs to the target site, such as nanoparticles, liposomes, vectosomes, spanlastics, micelles, dendrimers and implants are also discussed. Further, we also consider drug penetration enhancement approaches along with cutting-edge strategies for regaining vision during vision-threatening vascular degenerative disorders of the eye. Finally, challenges, such as ocular or even systemic complications associated with use of prolonged therapies and future prospects, such as combination of approaches with multidisciplinary integration to optimize delivery to the posterior eye are also addressed.
    Drug discovery today 04/2012; 17(13-14):748-59. · 6.63 Impact Factor
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    ABSTRACT: In the present work, concomitant use of self-microemulsifying drug delivery systems (SMEDDS) and a novel third-generation P-gp inhibitor, GF120918 (elacridar), for the effective transport of taxanes (paclitaxel and docetaxel) across an in vitro model of the intestinal epithelium and uptake into tumor cells were investigated. On the basis of solubility studies and ternary phase diagrams, different SMEDDS formulations of taxanes were prepared and characterized. In caco-2 cell permeation study, paclitaxel-loaded SMEDDS along with GF120918 showed a four-fold increase in apparent permeability, while docetaxel-loaded SMEDDS in combination with GF120918 showed a nine-fold increase in permeability, as compared to plain drug solution. Cell uptake studies on A549 cells were performed with microemulsions formed from both SMEDDS formulations loaded with rhodamine 123 dye and showed good uptake than plain dye solution. Confocal laser scanning microscopic images further confirmed the higher uptake of both SMEDDS formulations in the presence of GF120918.
    Journal of Microencapsulation 03/2012; 29(6):583-95. · 1.57 Impact Factor
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    ABSTRACT: Lumefantrine (LMF) is an antimalarial drug that exhibits poor oral bioavailability, owing to its poor aqueous solubility. To improve its antimalarial activity, nanopowder formulation using DYNO MILL was prepared. Combination of HPMC E3 (4%, w/v) and Tween 80 (2.5%, w/v) as dispersing agents, favored the production of smaller LMF particles with mean size of 0.251 μm. LMF nanopowder showed enhanced dissolution rate attributed to nanonization of LMF. The IC(50) value of nano-sized LMF was found to be 0.1 ng/mL, which was 175-times lower than the IC(50) value of unmilled LMF powder (17.5 ng/mL) and 42-times lower than the IC(50) value of chloroquine (4.2 ng/mL). The in vivo antimalarial activity demonstrated an enhanced antimalarial potential of LMF nanopowder against P. Yoelii nigeriensis compared to unmilled drug. Wet-milling using DYNO MILL offers a highly effective approach to produce stable drug nanopowders. Furthermore, LMF nanopowder makes the Coartem therapy more effective.
    Colloids and surfaces B: Biointerfaces 02/2012; 95:16-22. · 4.28 Impact Factor
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    ABSTRACT: 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 and analysis in positive ion mode. The method developed was validated in rabbit aqueous humor with a daily working range of 0.1–200 ng/mL with correlation coefficient, r > 0.999 and a sensitivity of 0.12 ng/mL as limit of quantification. The method proved to be accurate (recovery, 96.0–99.3%), precise (%RSD, ≤0.71%) and specific, and was applied to evaluate the moxifloxacin loaded nanoplexes (moxi-NPX) as vehicles for ocular drug delivery. Moxi-NPX (4037 ± 45.9 ng/mL. h) provided approximately five-fold increase in the relative ocular bioavailability compared with moxi solution (806.5 ± 32.5 ng/mL. h). In conclusion, moxi-NPX increases ocular bioavailability of moxi, prolong its residence time in the eye and are efficient ocular drug delivery vehicles.
    Journal of Liquid Chromatography &amp Related Technologies 01/2012; · 0.57 Impact Factor

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