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The present study investigates the screening of the formulation components as well as evaluates the quality issues of the nanostructured lipid carriers (NLCs) for the anticancer agent, CPT-11. The stepwise screening of the components for the preparation of NLCs requires the selection of liquid lipid or oil, based on the relative solubility of CPT-11 in different oils. Maximum solubility of the CPT-11 was found in capmul MCM-C8 (81±0.5 mg/ml). Hence, it was selected as the liquid lipid for the development of NLCs. Solid lipids gelucire 39/1, glyceryl mono stearate (GSM) and compritol ATO 888 were observed to have good affinity for the drug on systematic screening of different solid lipids. However, gelucire 39/1 and GSM were found to have lower physical compatibility (miscibility) with capmul MCM C-8. Hence, compritol ATO 888 was selected as the solid lipid phase for the preparation of NLCs. Ratio of liquid lipid (oil) to solid lipid was optimized with the intention of maximizing the oil concentration (as oil was found to have higher solubility of drug) as well as producing a lipid mix with sufficient melting point to maintain solid state. The liquid-solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (52.48±1.2 °C). Pluronic F-68 was selected as the main surfactant for the preparation of NLCs because of its good emulsification efficacy for the solid lipid liquid mix. The optimized formulation was also evaluated for the different quality issues. PXRD data revealed that the characteristic peaks of the compritol were present in the NLC samples and there was no appreciable polymorphic change when the formulation was stored for 6 months. Electron microscopic and DLS studies proved the absence of different colloidal species. Thermal analysis by DSC revealed that the lipid particles maintained sufficiently good melting point even after nanosizing. Absence of gelation on multiple syringing and resilience for the stress provided by autoclaving further established the quality of the developed NLCs.

Multidrug resistance (MDR) is an area of concern for the drug developers as well as clinical practitioners. This phenomenon is putting an emance pressure on treatment modalities of many diseases as well as posing a grave danger over clinically accepted drugs as well as molecules under clinical development. P-glycoprotein (P-gp) mediated efflux of xenobiotics is one of the major mechanisms involved in MDR. Hence, an effective modulation of P-gp may restore the potential of many substrate drugs. However, the non-specific P-gp modulation may be associated with many unwanted toxic effects. Therefore, an approach involving simultaneous exploitation of P-gp modulation as well as targeted delivery in a particulate carrier system may result in a more effective MDR reversal, accompanying a safer drug profile.

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.

Nanotechnology is the science that deals with structures in the size range of nanometers. It has the potential to greatly impact our lives. The employment of nanotechnology has opened new vistas in the areas of personalized health care, drug delivery, gene therapy, diagnostics, imaging, and novel drug discovery techniques. Enormous research is going on in the eld of nanotechnology to resolve various issues such as bioavailability, spatial and temporal delivery of drugs, and precise delivery of new molecules like genes and deoxyribonucleic acid (DNA). The delivery of therapeutic and diagnostic agents through the colloidal carriers is at the forefront of nanotechnology as it provides numerous opportunities for efcient exploitation of different formulations and routes of administration. In this perspective, rst, solid-core nanoparticles (NPs) were reported as an alternative drug carrier. NPs are dened as particulate dispersions or solid particles with a size in the range of 10-200 nm, built from macromolecular and/or molecular assemblies, in which the active principle is dissolved, dispersed, encapsulated, or even adsorbed or attached to the external interface. NPs are divided into two main classes based on their structures: nanospheres and nanocapsules that can be obtained by varying the methods of preparation. Nanospheres are matrix systems in which the drug is physically and uniformly dispersed and have a homogeneous structure, whereas nanocapsules are the systems in which the drug is conned in a cavity surrounded by a unique polymer membrane exhibit a typical core-shell structure (Figure 10.1). Their higher kinetic stability and rigid morphology are the major advantages over other colloidal drug delivery systems (such as liposome, niosome, microemulsions, nanoemulsions, etc.). Pharmaceutical NPs are one of the colloidal vehicles that possess the ability to carry drugs, accumulate preferentially at the target site, or release drugs in a controlled way within the body, which leads to improved pharmacokinetics and biodistribution of therapeuticagents with consequent reduction in systemic side effects and more efcient use of the therapeutic agents (Kreuter 1994; Alexis et al., 2008; Qi et al., 2012). They do not only allow the delivery of small drug molecules but are also expected to deliver peptides, proteins, and nucleic acids, hence opening the gate for gene therapy (Kim et al., 2005; Kommareddy et al., 2005; Jeon et al., 2012). NPs are usually administered through the parenteral route; however, because of their excellent barrier-crossing property, they are also being investigated for oral (Yin et al., 2007; Agueros et al., 2009; Kalaria et al., 2009; Jain et al., 2011), ocular (Motwani et al., 2008; Gupta et al., 2010; Basaran et al., 2011), nasal (Michael et al., 2009; Shahnaz et al., 2012), pulmonary (Ungaro et al., 2012), periodontal (Pinon-Segundo et al., 2005; Saboktakin et al., 2011), and transdermal (Elnaggar et al., 2011; Gupta and Vyas, 2012) routes. In spite of being a young technology, thousands of nanopharmaceuticals have been patented worldwide (Caruthers et al., 2007) and many have been approved by the Food and Drug Administration (FDA) for clinical purposes (Table 10.1).

Nanoparticles in Drug Delivery Systems Emilio Castro and Arun Kumar Synthesis and Characterization of Nanoencapsulated Drugs Arun Kumar, Ashley E. Saienni, and Niketa Dixit Nanoparticle Lung Delivery and Inhalation Aerosols for Targeted Pulmonary Nanomedicine Heidi M. Mansour, Chun-Woong Park, and Don Hayes, Jr. Biological Systems for the Delivery of Nanoparticles Niketa Dixit, Mark Glaum, Arun Kumar, and Don F. Cameron Nanodermatology: The Giant Role of Nanotechnology in Diagnosis and Treatment of Skin Disease Adam Friedman Nanoparticles for Drug Delivery of Small Molecules Ana Sofia Macedo and Eliana B. Souto Nanoparticle Therapies for Wounds and Ulcer Healing Chiara Gardin, Letizia Ferroni, Luca Lancerotto, Vincenzo Vindigni, Chiara Rigo, Marco Roman, Warren R. L. Cairns, and Barbara Zavan Nanoparticles in Bioimaging Javier L. Pou Ucha Nanoparticles in Anticancer Drug Delivery Frederic Lagarce Formulations of Nanoparticles in Drug Delivery Sushama Talegaonkar, Mohammad Tariq, and Zeenat Iqbal Nanoparticles for Ocular Drug Delivery Jaleh Barar and Yadollah Omidi Toxicology of Nanoparticles Siva K. Nalabotu and Eric R. Blough Animal and Cellular Models for Use in Nanoparticles Safety Study Kevin M. Rice and Eric R. Blough Index

Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review.

The objective of the study was to compare the complexing ability of Celecoxib with different complexing agents. Inclusion complex of Celecoxib is well established in literature but its evaluation in terms of thermodynamics was not studied elaborately. Hence after characterization of complexes with Differential scanning calorimeter, X-ray diffraction, NMR and % complexation efficiency, its solvation energetics and thermodynamics were determined. Complexation ability of celecoxib with caffeine was also evaluated, where non-inclusion (charge transfer) mechanism is involved. So, these two mechanisms of complexation were also tested with respect to each other. In this manuscript, new complexing agents (humic acid and fulvic acid) were also introduced for Celecoxib. These lie in the category of natural organic matter and we explored an indigenous source (Shilajit) to extract it. Other agents used for the development of complex were HP-β-CD and β-CD. Release mechanism of drug from complexes was studied by in vitro release studies. MTT assays were also performed to assess in vitro cell toxicity potential of the complexes in comparision to neat drug.

The singular aim of the proposed work is the development of a synergistic thermosensitive gel for vaginal application in subjects prone to recurrent vaginal candidiasis and other microbial infections. The dual loading of Itraconazole and tea tree oil in a single formulation seems promising as it would elaborate the microbial coverage. Despite being low solubility of Itraconazole in tea tree oil, a homogeneous, transparent and stable solution of both was created by co-solvency using chloroform. Complete removal of chloroform was authenticated by GC–MS and the oil solution was used in the development of nanoemulsion which was further translated into a gel bearing thermosensitive properties. In vitro analyses (MTT assay, viscosity measurement, mucoadhesion, ex vivo permeation, etc.) and in vivo studies (bioadhesion, irritation potential and fungal clearance kinetics in rat model) of final formulation were carried out to establish its potential for further clinical evaluation.

Irinotecan is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors. Hence, no oral formulation is marketed for Irinotecan till date. However, an optimized Self micro emulsifying drug delivery system (SMEDDS), formulated to produce nano range oil droplets by using P-gp modulator excipients can tackle the issue and elevate the systemic availability of Irinotecan. The present work focuses on the development of SMEDDS for Irinotecan and evaluation of its in vitro, ex vivo and in vivo potentials. The SMEDDS were developed using Capmul MCM-C8, Cremophor EL and Pluronic L-121 as oil, surfactant and co-surfactant respectively and has good oil carrying capacity (30%) with competence to produce nano-scale oil droplets (130 ± 2.13 nm) on spontaneous emulsification. A much deeper penetration to the intestine was observed with SMEDDS by using confocal laser scanning microscopy (CLSM). Flow-cytometric studies also revealed the greater uptake of fluorescent probe in Caco-2 cell-lines with the use of SMEDDS. Biochemical estimation of LDH from the intestinal tissues treated with SMEDDS and free drug suspension confirmed that the developed formulation is safe for use. Furthermore, the AUC 0 → t of Irinotecan from the optimized SMEDDS formulation was found to be 4 folds higher than that from Irinotecan suspension on oral administration. The optimized SMEDDS formulation was found to be capable of maintaining the sustained plasma drug level of Irinotecan with better bioavailability.

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.

In the present study an attempt has been made to load Poly (Lactic-Co-glycolic acid) microspheres with hydroxyapatite (HA) and ofloxacin and propose the composite microspheres to be used as local drug delivery system with the drug releasing capability for periodontitis treatment. A modified single emulsion method has been used for the preparation of microspheres. Experiments were conducted to optimize the formulation by RSM-Box-Behnken Method, which is an independent quadratic design involving three or four independent variables against a pre determined set of dependant parameters. The particle size of composite microspheres was analyzed and the average size was found to be 22.05 μm. Photomicrographs and scanning electron micrographs showed that the composite microspheres are spherical in shape and porous in nature. The microbiological activity of optimized formulation was evaluated using strain: S. aureus-ATCC- 29213 and E. coli–ATCC-25922. In vivo/in situ toxicity evaluation of the formulation was assessed by MTT assay and the formulation was found to be biocompatible.

Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing. An effective transdermal nano-emulsion drug delivery system can however resolve these issues effectively with greater therapeutic benefits and clinical significance. Therefore, the present work focuses precisely on pharmacokinetic, biochemical and mechanistic assessment of transdermal nanoemulsion gel in rats induced with Parkinson lesioned brain by 6-OHDA. DSC and FT-IR studies showed that NEG affects the normal lipid packing of stratum corneum to enhance the drug permeation. Study of pharmacokinetic parameters (AUC, C(max), and T(max)) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor). The AUC(0→∞) for RPCNG and RPTNG was found to be 928.07 ± 206.5 and 1055.99 ± 251.7 ngh/mL, respectively in comparison to 137.25 ± 31.3 and 467.15 ± 106.1 ngh/mL for RPG and oral tablet, respectively. The relative bioavailability of ropinirole has been enhanced more than two fold by RPTNG. Furthermore, antiparkinson activity was evaluated in terms of estimating the level of thiobarbituric acid reactive substances, glutathione antioxidant enzymes and catalase in lesioned brain of rats. Formulations were also found to be non-toxic and non-irritant by histological investigations.

The present study was aimed to assess the improvement of existing treatment regimens of Amphotericin B nanoconstrcuts which synergises with alginate for immunostimulation against visceral leishmaniasis. The particle size of Lip-nano (Plain AmB nanoconstructs) and Alg-Lip-nano (alginate capped Lip-nano) was 108.3 +/- 4.3 and 134.2 +/- 5.1 while zeta potential was (+) 28.4 +/- 3.3 and (-) 19.8 +/- 2.1 respectively. Percentage of parasite inhibition (intramacrophagic amastigotes) at 0.1 microg/ml conc. of AmB in case of Alg-Lip-nano (58%) was significantly higher (P = 0.05) compared to Lip-nano (48%). This supports that alginate coating over particles can activate macrophages to synergistically act with AmB in effective killing of parasite. This observation generates interest that immunotherapy with chemotherapeutic activity of AmB can effectively increase cure rate in visceral leishmaniasis.

This study was aimed to develop chitosan coupled lipid nanoparticle (Ch-Ptx-Lip), where immunomodulatory activity of chitosan and chemotherapeutic effect of paclitaxel can synergistically enhance efficacy of this novel drug delivery system. Particle size, zeta potential and % Entrapment Efficiency (%EE) of Ch-Ptx-Lip was found to be 113.3 +/- 4.5 nm (PDI: 0.38), (+)35.7 +/- 2.9 mV and 96.4 +/- 1.8% respectively. Morphological evaluation of these particles by TEM shows circular bilayer structure along with outer polymer layers. Ch-Ptx-Lip showed significantly enhanced cytotoxicity (p < 0.05) compared with marketed formulation (Ptx Solution) and Ptx-Lip when evaluated in-vitro by MTT assay on MCF-7 cell lines. Improved efficacy with lower dose of drug can be a new strategy against cancer with minimum side effects and shorter treatment duration.

Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms.

The purpose of the present study was to investigate the potential of nanoemulsions as nanodrug carrier systems for the percutaneous delivery of ropinirole. Nanoemulsions comprised Capryol 90 as the oil phase, Tween 20 as the surfactant, Carbitol as the cosurfactant, and water as an external phase. The effects of composition of nanoemulsion, including the ratio of surfactant and cosurfactant (S mix) and their concentration on skin permeation, were evaluated. All the prepared nanoemulsions showed a significant increase in permeation parameters such as steady state flux (J ss) and permeability coefficient (K p) when compared to the control (p

Ever since transdermal drug delivery came into existence, it has offered great promises, although most of them are yet to be fulfilled owing to some intrinsic restrictions of the transdermal route. On the positive side, transdermal drug delivery systems present advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The greatest hindrance in the percutaneous delivery is the obstruction property of the stratum corneum, the outermost layer of the skin, in addition to usual problems such as skin binding, skin metabolism, cutaneous toxicity and prolonged lag times.This paper reviews investigations on the feasibility and application of penetration enhancers as described in recent patents, which help in the selection of a suitable sorption promoter(s) for enhanced delivery of medicaments through the skin.The patents granted under various categories of penetration enhancers have been discussed including fatty acids, terpenes, fatty alcohol, pyrrolidone, sulfoxides, laurocapram, surface active agents, amides, amines, lecithin, polyols, quaternary ammonium compounds, silicones, alkanoates and so on.Scores of promising chemicals have been harnessed for their skin permeation promoting capacity as mentioned earlier. In future, many more chemicals and putative enhancers are likely be documented and patented.

Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms.

Considerable research efforts have been directed towards understanding the enigma of P-glycoprotein (P-gp) in drug development and delivery. P-gp is a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of various anti-cancer drugs. Modulation of this efflux transporter by various traditional 'chemosensitisers' forms a distinctive approach in improving pharmacokinetics and conquering drug resistance. However, such inhibitors show limitations associated with their safety and unwanted pharmacokinetic drug interaction restraining their clinical applicability. To address these concerns, several research groups have used pharmaceutical excipients (functional excipients or additives) to inhibit P-gp and enhance drug permeability. This article focuses on such excipients, various co-development strategies for the formulation of cytotoxic drugs with this multi-drug resistance (MDR) reversing additives.

Nanoemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water, and surfactants with a droplet size usually in the range of 10–100 nm (1,2). Their long-term stability, ease of preparation (spontaneous emulsification), and high solubilization of drug molecules make them promising as a drug delivery tool. They have found wide applications in oral drug delivery to enhance the solubility and bioavailability of the lipophilic drugs (3–5). Recently, there has been a surge in the exploration of nanoemulsions for transdermal delivery (6–8). They are also being investigated ardently for potential applications in ocular (9,10), pulmonary (11), nasal (12,13), vaginal (14,15), and parenteral drug delivery (16–18). The use of nanoemulsions in drug delivery has been reviewed, and it was noted that most studies have not been very systematic with regard to selection of surfactants and cosurfactants. The main objective of this study was to provide an efficient screening approach for the proper selection of oils, surfactants, and cosurfactants for the nanoemulsion formulation development. Ropinirole was selected as a model lipophilic drug for this purpose (Log P = 3.32). These systems often require high surfactant concentration, and this may lead to toxicity and irritancy problems. Therefore, judicious selection of surfactants along with their optimum concentration is required, which has been discussed in this report. Determination of the influence of the surfactant-to-cosurfactant mass ratio (Smix) on the nanoemulsion formation region also formed an important aspect of the study. Optimum selection would aid in better formulation with desirable attributes.

The aim of this work was to formulate transdermal therapeutic system (TTS) of an antihypertensive drug, enalapril maleate (EM) using a new penetration enhancer, piperidine hydrochloride (PH), belonging to the class of Dihydropyridines. The TTS of EM was prepared by solvent evaporation technique using polymers Eudragit E100 and polyvinyl pyrrolidone K-30 in varying ratios, 5% w/w dibutylphthalate as plasticizer and 10% w/w PH as penetration enhancer. The TTS was evaluated for in-vitro drug release using paddle over disc method and ex-vivo skin permeation using modified Keshary and Chein diffusion cell. The interaction studies were carried out by comparing the results of assay, UV and TLC analysis for pure drug and medicated and TTS formulation. Skin irritation potential of TTS was assessed by visual examination of treated rat skin. Stability studies were conducted according to ICH guidelines at a temperature of 40+/-0.5 degrees C and 75+/-5% RH. The optimized formulation was evaluated for preclinical bioavailability and antihypertensive efficacy using albino rat model. The optimized formulation provided 87.3% drug release in-vitro and a flux of 380 microg/cm(2)/hr over a period of 48 hours. No chemical interaction was found between the drug and excipients and there were no signs of skin irritation on application of patch. The optimized formulation was stable with a tentative shelf life of two years. Significant fall in BP (p

P-glycoprotein (P-gp) is found to play a very significant role in intestinal and biliary transport of irinotecan and its active metabolite, SN-38. This makes P-gp inhibition a logical strategy for improving irinotecan's oral efficacy and reducing its toxicity. The objective of the present study was to identify the most suitable P-gp inhibitor, amongst various commonly used herbal components via in vitro screening; followed by determination of in vivo effects in rats. Caco-2 cell monolayers were used to investigate the influence of various components (quercetin, hesperitin, piperine, curcumin and naringenin) on the transport of irinotecan. The secretory transport (basolateral-to-apical) was significantly decreased by all components (p

Multiple emulsions are complex polydispersed systems where both oil in water and water in oil emulsion exists simultaneously which are stabilized by lipophillic and hydrophilic surfactants respectively. The ratio of these surfactants is important in achieving stable multiple emulsions. Among water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) type multiple emulsions, the former has wider areas of application and hence are studied in great detail. Formulation, preparation techniques and in vitro characterization methods for multiple emulsions are reviewed. Various factors affecting the stability of multiple emulsions and the stabilization approaches with specific reference to w/o/w type multiple emulsions are discussed in detail. Favorable drug release mechanisms and/or rate along with in vivo fate of multiple emulsions make them a versatile carrier. It finds wide range of applications in controlled or sustained drug delivery, targeted delivery, taste masking, bioavailability enhancement, enzyme immobilization, etc. Multiple emulsions have also been employed as intermediate step in the microencapsulation process and are the systems of increasing interest for the oral delivery of hydrophilic drugs, which are unstable in gastrointestinal tract like proteins and peptides. With the advancement in techniques for preparation, stabilization and rheological characterization of multiple emulsions, it will be able to provide a novel carrier system for drugs, cosmetics and pharmaceutical agents. In this review, emphasis is laid down on formulation, stabilization techniques and potential applications of multiple emulsion system.

A simple, sensitive, selective, precise and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for densitometric determination of moxifloxacin both as a bulk drug and from pharmaceutical formulation was developed and validated as per the International Conference on Harmonization (ICH) guidelines. The method employed TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase and the mobile phase consisted of n-propanol-ethanol-6M ammonia solution (4:1:2, v/v/v). Densitometric analysis of moxifloxacin was carried out in the absorbance mode at 298 nm. Compact spots for moxifloxacin were found at R(f) value of 0.58+/-0.02. The linear regression analysis data for the calibration plots showed good linear relationship with r=0.9925 in the working concentration range of 100-800 ng spot(-1). The method was validated for precision, accuracy, ruggedness, robustness, specificity, recovery, limit of detection (LOD) and limit of quantitation (LOQ). The LOD and LOQ were 3.90 and 11.83 ng spot(-1), respectively. Drug was subjected to acid and alkali hydrolysis, oxidation, dry heat, wet heat treatment and photodegradation. All the peaks of degradation products were well resolved from the standard drug with significantly different R(f) values. Statistical analysis proves that the developed HPTLC method is reproducible and selective. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. Moreover, the proposed HPTLC method was utilized to investigate the kinetics of the acidic and alkaline degradation processes at different temperatures. Arrhenius plot was constructed and apparent pseudo-first-order rate constant, half-life and activation energy were calculated. In addition the pH-rate profile for degradation of moxifloxacin in constant ionic strength buffer solutions within the pH range 1.2-10.8 was studied.

Ganciclovir (GCV) plays an important role in the treatment of ocular viral infections. A high dose results in dose-related toxicity including bone marrow suppression and neutropenia. The aim of the present study was to investigate the comparative potential of different mucoadhesive nano formulations for the topical ocular delivery of Ganciclovir. GCV mucoadhesive Nanoemulsions (GCV-NEs), chitosan nanoparticles (GCV-NPs), GCV mucoadhesive niosomal dispersion (GCV-NDs) were prepared by the reverse-phase evaporation technique. All of the three formulations were evenly round in shape with mean particle size in the range of 23-200 nm. These results indicated the nonirritant and nontoxic nature of the developed formulations. The achieved results may be useful for formulation development of GCV, which could be effective in the treatment of ocular infections by topical instillation.

Development of an effective formulation involves careful optimization of a number of excipient and process variables. Sometimes the number of variables is so large that even the most efficient optimization designs require a very large number of trials which put stress on costs as well as time. A creative combination of a number of design methods leads to a smaller number of trials. This study was aimed at the development of nanostructured lipid carriers (NLCs) by using a combination of different optimization methods. A total of 11 variables were first screened using the Plackett-Burman design for their effects on formulation characteristics like size and entrapment efficiency. Four out of 11 variables were found to have insignificant effects on the formulation parameters and hence were screened out. Out of the remaining seven variables, four (concentration of tween-80, lecithin, sodium taurocholate, and total lipid) were found to have significant effects on the size of the particles while the other three (phase ratio, drug to lipid ratio, and sonication time) had a higher influence on the entrapment efficiency. The first four variables were optimized for their effect on size using the Taguchi L9 orthogonal array. The optimized values of the surfactants and lipids were kept constant for the next stage, where the sonication time, phase ratio, and drug:lipid ratio were varied using the Box-Behnken design response surface method to optimize the entrapment efficiency. Finally, by performing only 38 trials, we have optimized 11 variables for the development of NLCs with a size of 143.52 ± 1.2 nm, zeta potential of -32.6 ± 0.54 mV, and 98.22 ± 2.06% entrapment efficiency.

There has been keen interest in the development of a novel drug delivery system. Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and channel the active entity to the site of action. At present, no available drug delivery system behaves ideally achieving all the lofty goals, but sincere attempts have been made to achieve them through novel approaches in drug delivery. A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve controlled and targeted drug delivery. Encapsulation of the drug in vesicular structures is one such system, which can be predicted to prolong the existence of the drug in systemic circulation, and reduce the toxicity, if selective uptake can be achieved. Consequently a number of vesicular drug delivery systems such as liposomes, niosomes, transfersomes, and pharmacosomes were developed. Advances have since been made in the area of vesicular drug delivery, leading to the development of systems that allow drug targeting, and the sustained or controlled release of conventional medicines. The focus of this review is to bring out the application, advantages, and drawbacks of vesicular systems.

The present work deals with various attempts to prepare a gastroretentive formulation of lacidipine for treating gastroparesis. High density sucrose beads were modified by coating with certain polymers, but unfortunately sustained release could not be achieved. Granules were prepared by wet granulation technology using different combinations of polymers and a release of the drug was observed. The method failed to release the drug as per desired specifications. Polymeric coating followed by wet granulation was thought to be a better process to sustain thedissolution rate. The release rate can be modified by the incorporation of different polymeric coatings, but the mucoadhesive potential of granules was only 4.23% which might be due to its large size and the presence of other ingredients. Further, the lacidipine loaded microparticles were prepared by different methods such as compression, ionic gelation with TPP, ionic gelation with TPP and glutaraldehyde, spray drying and coacervation techniques. The formulations were evaluated for average particle size, surface morphology, entrapment efficiency, % yield and mucoadhesive potential. The microparticles prepared by compression method using HPMC K4M and SCMC as mucoadhesive polymers and BaSO4 as high density diluent showed poor bioadhesion (8.3%) and poor release characteristics (100% in 120min). Ionic gelation with tripolyphosphate yielded microspheres with poor mechanical strength. In order to improve its mechanical strength, TPP ionic gelation was combined with step-wise cross-linking with glutaraldehyde. The additional solidification step to improve mechanical strength left this procedure tedious, time consuming and cytotoxic. Spray drying method gave a very low yield with 46.67% bioadhesion. The method using CaCl2 for ionotropic gelation showed the best results with regard to physical characteristics (well formed discrete, spherical surface microcapsule), particle size (88.57±0.51), in vitro bioadhesion (67.33%), yield (>85%) and loading (>70%).

The present work is aimed to develop a simple, sensitive, robust and reliable HPLC method for the estimation of irinotecan in the physiological media in order to assess the permeability profile of irinotecan, using the everted gut sac, in the presence of various P-gp modulators. Separation was achieved using, C18 column with mobile phase consisting of acetonitrile and 0.045 µM sodium dihydrogen phosphate dihydrate buffer containing ion pair agent heptane sulphonic acid sodium salt (0.0054 µM), pH 3. The flow rate was maintained at 1 ml/min and analysis was performed at 254.9 nm using PDA detector. Calibration data showed an excellent linear relationship between peak-area verses drug concentration (r(2), 0.9999). Linearity was found to be in the range of 0.060-10.0 µg/ml. Limits of detection and quantification were found to ~0.020 µg/ml and ~0.060 µg/ml, respectively. The developed method was found to be precise (RSD < 1.5%, for repeatability and

Ceramic nanoparticles are primarily made up of oxides, carbides, phosphates and carbonates of metals and metalloids such as calcium, titanium, silicon, etc. They have a wide range of applications due to a number of favourable properties, such as high heat resistance and chemical inertness. Out of all the areas of ceramic nanoparticles applications, biomedical field is the most explored one. In the biomedical field, ceramic nanoparticles are considered to be excellent carriers for drugs, genes, proteins, imaging agents etc. To be able to act as a good and successful drug delivery agent, various characteristics of nanoparticles need to be controlled, such as size range, surface properties, porosity, surface area to volume ratio, etc. In achieving these properties on the favourable side, the method of preparation and a good control over process variables play a key role. Choosing a suitable method to prepare nanoparticles, along with loading of significant amount of drug(s) leads to development of effective drug delivery systems which are being explored to a great extent. Ceramic nanoparticles have been successfully used as drug delivery systems against a number of diseases, such as bacterial infections, glaucoma, etc., and most widely, against cancer. This review gives a detailed account of commonly used methods for synthesising nanoparticles of various ceramic materials, along with an overview of their recent research status in the field of drug delivery.

Cancer treatment, owing to its myriad limitations, has often been a formidable challenge to both the practitioners as well as researchers. There has been a continued effort in designing newer and successful strategies to obtain optimal results. One such strategy includes the elucidation of a combinatorial approach of the conventional chemotherapy protocol with various mechanophysical methods. This opinion article discusses that how two thrust areas like targeting cancerous cells using a novel drug-delivery system and mechanophysical methods of killing them can be amalgamated into a complete new vector, which is driven with precision, specificity, accuracy, and better efficacy. This approach relies on devising a mechanophysical responsive vehicle, which could be added to other anticancer therapies. The new combined tool would then kill the cancer cells not just by releasing the chemotherapeutic drug at the desired site but also by killing individual cells through the purported mechanophysical stimuli. Summarily, the resultant vector generates an angle influenced by the direction of the mechanophysical vector, leading to a better therapeutic modality.

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 is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport. Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the feasibility and application of flavonoids as P-gp modulators for improved efficacy of anti-cancer drugs like taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids. The review also focuses on flavonoid-drug interactions as well as the reversal activity of flavonoids useful against MDR. In addition, the experimental models which could be used for investigation on P-gp mediated efflux are also discussed.