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Pomegranate seed oil with its high levels of phenolic compounds is known to exhibit neuroprotective effects. Delivering hydrophilic drugs to the brain is challenging since blood–brain barrier allows only a few lipophilic molecules into the brain, thus posing an additional barrier for drug delivery to the brain in conditions like Alzheimer’s. The present study focuses on the preparation of the stable galantamine hydrobromide (GHBr) microemulsion (ME) using pomegranate seed oil (PSO) as an adjuvant. The developed ME was characterized for various physicochemical properties, cytotoxicity, and protective role against Amyloid Beta (1–42) oligomer-induced toxicity in IMR 32 cell line. GHBr and PSO ratio was optimized based on an in-vitro diffusion study and compatibility study using DSC and FTIR. The ME was prepared by the water titration method and optimized using the one variable at a time (OVAT) strategy. Globule size and PDI of GHBr PSO ME were found to be 200.36 ± 0.01 nm, and 0.219 ± 0.011 nm respectively. GHBr PSO ME showed significantly better results in terms of cell line toxicity, antioxidant activity and protective effect against Aβ induced cell death. The results obtained showed the potential of using PSO as an effective synergistic agent along with the anti-Alzheimer’s drug for the treatment of disease.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With this backdrop, in present review, we have reemphasized the role of mitochondria in cancer progression and inhibition, highlighting the different targets that can be explored for targeting of disease. Moreover, we have also summarized different nanoparticulate systems that have been used for treatment of cancer via mitochondrial targeting., Graphical abstract Image, graphical abstract

The aim of the present study was to investigate increase in delivery of drug upon formulation as mucoadhesive microemulsion system and further to investigate possibility of any cytotoxic effects using such formulation.Considering hydrophilic and small molecular nature of the drug, it was attempted to be formulated as microemulsion, by using pseudo ternary phase diagram method. Thus, three types of microemulsions were prepared; oil in water, water in oil type and chitosan-coated microemulsion. These microemulsions were characterized for several physicochemical properties like size, zeta potential, Polydispersity index, and compared for in vitro cell viability and ex vivo corneal irritation study.All three microemulsions were quite stable, transparent and homogenous systems. They showed similar drug release pattern, but highest ex vivo goat corneal permeation was observed with Chitosan coated microemulsion when compared with ganciclovir solution.All microemulsions were found to be non-irritant in in vitro cell viability assay and ex vivo corneal irritation study, indicating the potential of using such systems for delivery of drug to eye.

Present work investigates the possibility of a polyethyleneglycolylated (PEGylated) microemulsion (ME) to deliver drug to the posterior segment of eye. Triamcinolone acetonide (TA), a widely used drug in intraocular diseases, was selected as the model drug. Based on solubility and emulsification capacity, components of microemulsion were selected and optimum formulation was obtained using a pseudoternary phase diagram. The optimized ratio of Capmul MCM C8 (oil): AccononMC8-2 (surfactant): Transcutol (cosurfactant): deionized water was 5:35.5:4.5:55. This was further PEGylated using 1,2-distearoylphosphatylethanolamine-polyethyleneglycol 2000 (DSPE-PEG 2000). This PEGylated ME loaded with TA was characterized and evaluated in vitro, ex vivo, and in vivo for topical ocular use. The developed PEGylated ME loaded with TA was homogenous, stable, and nonirritable to eye and had the ability to reach the posterior segment of eye on topical instillation.

The present study investigates the role of fish oil (FO)- and butter oil (BO)-enriched microemulsion-based system of galantamine hydrobromide (GH), an anti-Alzheimer drug, for its potential role in brain permeation enhancement and neuroprotection against oxidative stress. Microemulsion (ME)-based system of GH was prepared using water phase titration. The prepared ME was characterized by several physicochemical parameters like particle size, polydispersity index, and ex vivo drug permeation. Cell-based oxidative stress assays and pharmacokinetic studies were performed using C6 glial cell lines, and Sprague Dawley rats, respectively. The optimized ME comprised 5.3% v/v of Capmul MCM EP (as oil),15.8% v/v of Tween-80 (as surfactant), 5.3% v/v of Transcutol P (as co-surfactant), and 73.6% v/v of water (as aqueous phase). The addition of FO and BO resulted in a slight increase in the droplet size and decrease in transparency of ME. Cell-based anti-oxidative stress assays (glutathione assay, nitrite assay, and lipid peroxidation assay) showed the efficacy of formulation in the order of ME, BO ME, and FO ME, respectively. A similar trend was also observed in in vivo animal studies, wherein GH FO ME showed a comparatively higher percentage of drug reaching the brain when administered by intranasal route than by IV route. The study concluded the potential benefits of co-administering FO- and BO-enriched microemulsion is not only enhancing the permeation of drugs across BBB but also improving efficacy against lipopolysaccharide-induced oxidative stress. Graphical abstract.

Dexamethasone (Dex) is one of the most commonly used anti-vascular endothelial growth factor (anti-VEGF) drugs being used in ocular diseases whether it is associated with anterior segment or posterior segment. For diseases of posterior segment of eye, Dex is delivered as intravitreal implant but the route used for the same is very invasive and poses several hazards on long term use. Thus, topical formulation with ability to outreach retina from ocular surface was intended. Thus, polyethylene glycolylated (PEGylated) microemulsion (ME) was attempted as it can cross the membranous barrier of eye (cornea, conjunctiva, and sclera) and remain afloat in fluidic barrier (aqueous humor, choroid, etc.) as well. Present investigation involved development of Dex-loaded PEGylated ME which was stable, non-toxic to ocular surface, capable to cross cornea and enhanced residence as well as availability of loaded drug in retina. The developed PEGylated ME had physicochemical properties like size (15.98 ± 3.05 nm), polydispersity index (0.25 ± 0.04), zeta potential (-0.04 ± 0.47 mV), percentage transmittance (99.84 ± 1.17%), and drug content (99.32 ± 3.21%). It showed sustained Dex release in

Purpose: Androgenic alopecia (AGA) is a condition of progressive hair loss and involves follicular miniaturization triggered mainly due to varying levels of androgen besides environmental and genetic factors, which may also play some role. Minoxidil (MXD) has been considered as most effective therapeutic moiety to treat this disorder. Another drug Tretinoin (TRET) is known for its comedolytic activity and is reported to enhance percutaneous absorption of MXD. Presently both these drugs are being utilized for treatment of androgenic alopecia (AGA) in solution form which poses several problems in terms of poor solubility of drug, frequency of application and side effects. Materials and methods: Current work investigates liposomal hydrogel system for simultaneous delivery of MXD and TRET to overcome the limitations of existing formulation. Successful development of liposomes was commenced by thin film hydration method and various parameters affecting desired characteristics like size, morphology, entrapment efficiency; stability and ex vivo permeation were optimized. The formulated liposomes were further characterized for various physicochemical properties and evaluated for in vivo irritancy study in animals. Results and discussion: Results suggested prepared liposomes to be stable, homogenous and capable to hold both the drugs within. Association with hydrogel enhanced the permeation of MXD through skin ex vivo but TRET retained on the skin. Liposome loaded hydrogel was found to be non-irritant to skin. Conclusion: Overall developed system showed potential for effective and simultaneous delivery of both the drugs.

Objective: Repaglinide is a well-known FDA approved drug from category of meglitinide; used for the treatment of diabetes. However, its use is limited because of its poor water solubility which lea...

Aim: Utility of cow ghee (CG) as permeation enhancer in development of topical ocular microemulsion (ME) for delivery of fluocinolone acetonide (FA) to posterior eye.Methods: For ME prepara...

Permeability glycoprotein (P-gp) is a 170 kDa membrane transporter from the category of efflux pumps, which is situated at the apical site of epithelial membrane. P-gp is known to efflux diverse classes of chemical compounds including anticancer agents, antibiotics, steroidal compounds and many more. Numerous strategies have been used to inhibit the efflux of such compounds via efflux transporters including co-administration with P-gp inhibitors, chemical modifications and others, with limited success. Excipients (so called inactive ingredients) are intentionally added in drug formulations to alter characteristics of drug. Nowadays, there is increasing interest in investigating these traditionally used excipients for their efflux pump inhibitory potential, as they have been reported to cause subtle changes, that can affect transporter proteins (efflux pumps) on cell membrane. Many reviews have explained the role of specific P-gp inhibitors for improved drug delivery, however there is not much data when it comes to exploring an excipient for its inherent function and P-gp inhibitory potential. This review will shed light on current status of excipients, which can be used to modulate membrane transporter inhibition potential and discuss the mechanism involved in it. Certain preparations, formulated using such excipients which enhances drug absorption and minimize related toxicity, will be also discussed.

This review describes current nanotechnology-based delivery systems for ocular targeting. Amongst all the drug delivery systems existing today, ocular drug delivery is one such delivery approach which is having great endeavours due to the challenges faced by it. Many new as well as exciting treatment options have emerged in this field. The major cause behind development of new treatment alternatives in this field are the limitations raised by the conventional approaches. Currently, researchers are working on development of novel nano techniques to overcome these challenges. The major hurdle is associated with the complicated anatomy and physiology of eye having various static (cornea, conjunctiva, retinal pigmental epithelium) as well as dynamic barriers (blood aqueous barrier, blood retinal barrier) which reduce the overall bioavailability of the drugs. These membranous and fluidic barriers make drug delivery to eye a very challenging task. Hence, current research focuses on developing a system, which is least invasive and able to surpass ocular barriers to maintain sufficient drug levels within the ocular tissue. Nanotechnology based delivery systems play a vital role in this. Many vesicular as well as particulate systems are attempted for the same for anterior as well as posterior segment targeting which can easily overcome limitations of conventional drug delivery systems. Current momentum and ongoing research in this field holds a significant level of promise towards development of improved therapies for treating vision related ailments.

Dissolution has become an indispensable tool to predict the in vivo performance of dosage form, especially in recent times, because of the increasing complexity of new drugs discovered. Several attempts have been made to modify dissolution, so that it mimics the in vivo behavior to maximum possible accuracy and minimizes the probability of in vivo bioequivalence failures. In this context, several advancements have been reported including drug dissolution/absorption simulating system, bionic system, dissolution/permeation model, biphasic dissolution system, Caco-2 cell monolayer in combination with compendial dissolution apparatus, artificial stomach duodenum model, dynamic gastric model, Netherlands Organization for Applied Scientific Research gastrointestinal model, and many more. The present review highlights the recent advancements in dissolution methods with a focus on in vivo predictive dissolution methods, their advantages and disadvantages, and key factors governing the results obtained. The impact of maintaining sink conditions and use of biorelevant media is also discussed briefly.

The objective of present study was to optimize spray drying of Risperidone (RIS) nanosuspension for achieving lower particle size, higher yield and good compressibility of spray dried powder using Quality by design approach. RIS nanosuspension was prepared by anti-solvent precipitation technique using poloxamer 68 and Poloxamer 127 as stabilizers. 3 level 2 factorial design was applied using two independent factor variables viz., X1: feed pump speed (RPM) and X2: inlet temperature (oC) and their effect upon dependent variables viz., Y1: Size, and Y2: %Entrapment efficiency was determined at three different levels. Spray dried powder was further characterized for bulk level properties and formulated as an orally dispersible tablet (ODT). The developed ODT were characterized by various parameters like wetting time, disintegration time, hardness, friability, weight variation and dissolution for comparison. Size and PDI of formulated RIS Nanosuspension were found to be 200.00 ± 0.40 nm and 0.210 ± 0.03 respectively. Optimized process parameters for spray dryer were obtained from design space, which gave critical quality attributes (CQA) response of lowest size and highest yield of 214.21 ± 2.01 nm and 61.85 ± 1.02% respectively. FTIR, DSC, XRD and AFM studies of spray dried RIS nanosuspension revealed that crystallinity of RIS was altered during spray drying process. Bulk density, Tapped density, Hausner ratio, Compressibility index and Angle of repose of spray dried RIS was found to be 0.588 ± 0.12 g/mL, 0.641 ± 0.20 g/mL, 1.09 ± 0.26, 8.33 ± 0.32 and 32.40o ± 0.98o respectively. ODT formulated using optimized spray dried nanosuspension showed higher dissolution than marketed ODT formulation which may be due to increase in solubility of Risperidone during spray drying of nanosuspension.

Background Treatment in neurological disorders like schizophrenia requires continuous presence of drug in the brain for a prolonged period of time to achieve an effective therapeutic response. Delivery of antipsychotic drug quetiapine in the form of conventional delivery systems suffers from low oral bioavailability, first-pass metabolism, and frequent dosing. In addition to that biological obstacles present at the brain interface also hinders the transport of quetiapine across the brain. In the present study, nasal delivery of quetiapine loaded nanoparticles and microemulsion formulation were designed to evaluate their individual in vivo potential to achieve brain targeting. Chitosan-based polymeric nanoparticles and mucoadhesive microemulsion systems were developed through ionic gelation and water titration method respectively. Results Microemulsion showed globule size lower than 50 nm with 95% drug loading while, nanoparticles exhibited 65% drug loading with particle size of 131 nm. Nasal diffusion study showed highest diffusion with chitosan-based mucoadhesive microemulsion over nanoparticles suggesting permeation-enhancing effects of chitosan. Due to the overall hydrophilic nature, quetiapine-loaded nanoparticles could not diffuse superiorly across nasal mucosa, hence, showed 1.3 times lesser diffusion compared to mucoadhesive microemulsion. Pharmacokinetics in rats showed highest brain concentration and 1.9-folds higher nasal bioavailability with mucoadhesive microemulsion over nanoparticles suggesting direct brain transport through olfactory route bypassing blood-brain barrier. Conclusion Higher quetiapine transport with mucoadhesive microemulsion suggested that synergistic effects like tight junction modulation by chitosan and unique composition facilitating smaller globule size could be responsible for higher brain transport. Imaging study by gamma scintigraphy also supported pharmacokinetic outcomes and concluded that mucoadhesive microemulsion could be a promising nanocarrier approach for non-invasive nose to brain delivery. Graphical abstract

Major depressive disorder (MDD) or depression is a heterogeneous mental illness which have direct effect on patient’s behavior and cognition; causing constant feeling of unhappiness and loss of concern in earlier enjoyed events. Vortioxetine (VOR) is a new atypical serotonergic antidepressant reported for the treatment of major MDD and has its use in various psychological disorders. Despite its therapeutic potential, it has poor water solubility which creates problem in delivery. Nanocrystal based orally disintegrating tablets (ODTs) are proposed to enhance water solubility and dissolution rate of VOR. Nanosuspension was prepared by nanoprecipitation method after optimizing various parameters. The formulated nanosuspension was effectively converted to solid powder by the lyophilization technique with emphasis on parameters like nature/concentration of cryoprotectants. Prepared nanocrystals were characterized for solid state of drug present, morphology, size after re-dispersion and stability. The powders were then subsequently compressed into ODTs and dissolution profiles of the tablets were compared. The dissolution profile of the ODTs prepared from nanocrystals showed superior dissolution profile in comparison to ODTs prepared from untreated drug.

Successful treatment of pathologies affecting eye depends on inherent activity of the drug, its ability to cross several ocular barriers in order to reach biophase and most importantly its maintenance in the biophase for prolonged period. The present chapter on ocular drug delivery system (ODDS) gives an insight on different types of ocular dosage forms, ranging from simple sterile eye drop for the ocular surface to complex implants for intraocular tissue, meant for instilling, administering or delivering drug to eye. The different barriers which these delivery system needs to surmount, had been discussed briefly with insights on different types of commercially available simple and complex ocular formulations. Advancement in traditional ocular delivery system with emphasis on minimizing precorneal losses using bioadhesives or penetration enhancers and advanced corneal delivery systems like nanoparticulate systems, liposomal delivery systems, iontophoresis-based devices, punctal plugs, nano implants, etc. had been also discussed. An overview of recently patented formulations, meant for ocular pathologies that are not amenable to topical drug delivery, are also highlighted to stimulate further research in the unexplored arena of ocular drug delivery. This concise information on current research and development efforts in the area of ocular delivery will be of tremendous help to design better therapeutic systems for various ailments and disorders affecting eye.

Nose is the only place where the brain “meets the outside world” and thus offers a huge window of opportunity to target a vast range of neurotherapeutics to the brain. Delivery of drugs to the brain especially via the nasal route requires a thorough understanding of various anatomical (nasal cavities, vestibules, olfactory, respiratory region, etc.) and physiological barriers (blood flow and lymphatic system, nasal valve and aerodynamics, mucociliary clearance, etc.) a drug has to surmount in nose, before it can successfully reach the target site. Besides these nasal barriers, in order to reach brain, additional barriers in brain, namely, blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), further hinder the delivery of drugs in required concentration at the target site. The objective of this chapter is to provide a thorough understanding of these barriers’ properties in order to design an efficient drug delivery system that can efficiently overcome these hurdles.

Electrohydrodynamic techniques are promising tools for fabricating drug delivery system in one-step process with numerous advantages like high loading capacity, ease of operation, high encapsulation efficiency, simultaneous delivery of more than one active entities/drugs, and cost-effectiveness. With increasing incidences of solubility and dissolution-related problems posed by poorly soluble drugs, electrospraying offers an added avenue of modulating particulate level properties of drug, thus enhancing surface area, solubility, and dissolution rate. Further with the advent of therapeutics like siRNA, genes, coenzymes, and plasmid DNA, etc., opportunities for electrohydrodynamics-based delivery system will continue to flourish. This necessitates the need to have better understanding of various formulation-related and process-related parameters, critical to electrospraying, which may affect the output. Though there are concerns regarding the extent to which protein or DNA can maintain their structure under the influence of high voltage and remain viable, but for small molecules, electrospraying has shown tremendous potential as a technique, which can produce monodisperse particles having distinct morphology. Such particles with distinct surface features can be customized for site-specific delivery. Further to fortify the benefits offered by electrospraying and take it to the next level of translation, it is required that existing process- and product-related bottlenecks are minimized and supported through clinical studies. If implemented, the above measures will surely go a long way to establish electrospraying as an indispensable technique in the field of drug delivery.

In order to investigate the possible role of butter oil (BO) and omega-3 fatty acids-rich fish oil (O3FO) in the delivery of donepezil hydrochloride microemulsion (DH-ME) to the brain via intranasal route, the present study was conducted. DH:BO and DH:O3FO binary mixtures (9:1 to 1:9) were prepared by simple physical mixing and subjected to in vitro diffusion study. Ratios of DH:BO and DH:O3FO, which showed the highest diffusion, were selected for further development of microemulsion (ME). Globule sizes of DH-BO-ME and DH-O3FO-ME were found to be 87.66 ± 5.23 nm and 88.59 ± 8.23 nm, respectively. Nasal histopathological study and in vitro cytotoxicity study revealed the safety of the formulation. Higher percentage of nasal diffusion was found with DH-BO-ME (71.22 ± 1.21%) and DH-O3FO-ME (62.16 ± 1.23%) in comparison to DH-ME (59.69 ± 1.74%) and DH solution (55.01 ± 1.19%), which was further supported by in vitro cell permeability study. After intranasal administration, %bioavailability of drug in the rat brain (Sprague-Dawley rats)(on the basis of DH-ME IV) was higher with DH-BO-ME (313.59 ± 12.98%) and DH-O3FO-ME (361.73 ± 15.15%) in comparison to DH-ME (168.62 ± 6.60%) and DH solution (8.960 ± 0.23%). The results of ex vivo diffusion study and in vivo pharmacokinetic study suggested that BO and O3FO helped in enhancing the nasal permeability and the brain uptake of drug when administered intranasally.

Objective Design, develop, optimize and validate a chronotherapeutic double coated aceclofenac pellet formulation prepared using extrusion-spheronization technique for effective palliative action of RA symptoms. Significance RA is a chronic systemic autoimmune disease leading to pain in joints, connective/fibrous tissues, cartilages, ligaments, muscles and tendons. RA mostly prevails at productive age of human life and its chronic effect may lead to deformity or disability thereby resulting in substantial socioeconomic burden. Early morning circadian manifestations of symptoms in RA are due to night time activation of inflammatory responses. Chronotherapeutic double coated pellet formulation can deliver aceclofenac according to circadian rhythm of RA symptoms leading to effective palliative action. Methods Core aceclofenac pellets were prepared and double coated with inner swellable HPMC and outer erodible ethylcellulose layers to achieve desired lag time in ACE release. Formulation and process parameters of double coating process were optimized by QbD approach. Drug release lag time, production yield and pellet morphology were identified as CQAs. Results In vitro drug release and in vivo pharmacokinetic studies revealed that optimized pellet formulation with 15% weight gain due to swellable layer, 1.6% weight gain due to erodible layer and 5% of pore forming agent exhibited highest desirability indices with drug release lag time of 5h, production yield of 79 ± 2%, 1.05 ± 0.04 aspect ratio, 88.1% ± 1.25% roundness and. 1.22 ± 0.2 mm pellet size. Conclusion Desired ACE release lag time required to match the circadian rhythm of RA was achieved through double coated spheronized pellets, without any associated drawback of dose dumping.

Olanzapine (OLAN) as an antipsychotic agent has shown its potential in effective management of psychotic disorders however its use is limited because of its poor water solubility. The aim of present work was to improve solubility of OLAN by developing a stable nanocrystal based orally disintegrating tablets (ODTs), using hyperomellose as potential stabilizer. Comparative evaluation of electrospraying and lyophilization as solidification techniques was carried out to assess its effect on solid state properties of OLAN nanocrystals before transformation to ODTs. OLAN Nanosuspension was developed using antisolvent precipitation method and exhibited particle size, polydispersity index and zetapotential value of 223.1 ± 1.5 nm, 0.105 ± 0.4 and −17.9 ± 3.5 mV respectively. Solid powders obtained from both the solidification techniques were compared in terms of size after re-dispersion, particle morphology, surface area, pore volume and solid state of drug present. Subsequently ODTs were prepared from these powders with needful excipients and % amount dissolved was evaluated. Rate of dispersion was found to be higher for ODTs prepared using lyophilized powder (∼84% in 5 min) while other characterization parameters were comparatively similar. Overall, Lyophilization resulted in powders with better bulk level properties in comparison to electrospraying process.

Controlled release dosage forms are essential when the drug release rate impacts the effectiveness of therapy. In the present study, a modified-release dosage form of domperidone was developed in the form of pellets, which were subsequently compressed into a tablet to disintegrate and be swallowed by patients, without changing the release profile. Sustained-release pellets of domperidone prepared by the extrusion-spheronization and layering technique using Celphere® 102 (microcrystalline cellulose spheres) and Suglet® (sugar spheres) as core seed, subsequently coated with Kollicoat® SR 30 D (polyvinyl acetate dispersion) as rate controlling polymer, were developed using the multiple unit pellet system (MUPS) as a plateform technology. Then, 2ˆ3 full factorial design (two level and three parameters) was applied to assess the impact of the different variables on the properties of the resulting pellets prepared by extrusion-spheronization. Different types of tableting excipients were combined for better pellet compressibility. The combination of Ceolus® granules (granules prepared using a fibrous grade of microcrystalline cellulose) and Ludipess® (lactose based co-processed excipient) was found as a suitable tableting excipient for MUPS preparation. The MUPS based sustained-release domperidone formulation prepared using Celphere® 102 was found to possess rapid disintegration properties, hardness, and unaltered release profile even after compression.

Purpose of the present investigation was to explore the potential of butter oil (BO) as a novel permeation enhancer to enhance the drug concentration in the brain when given intranasally. Quetiapine fumarate (QF) was selected as a model drug since it undergoes extensive first-pass metabolism leading to poor oral bioavailability of 9%. QF:BO binary mixture was prepared by simple physical mixing in the ratio of 1:9 to 9:1. Diffusion study was performed to obtain optimized QF:BO ratio. QF loaded microemulsion (ME) system (QF ME) was developed by water titration method. The optimized ratio of QF:BO showing higher permeation for QF was added into ME to obtain QF:BO ME. Globule size of QF ME and QF:BO ME was found be 61.59 ± 0.54 and 133.30 ± 1.74 nm, respectively. Nasal diffusion data revealed that QF:BO ME showed higher permeation (85.45 ± 2.14%) for QF in comparison to QF ME (52.07 ± 2.07%) and QF solution (40.00 ± 2.01%). Nearly 4.6 folds higher brain bioavailability of QF:BO ME (384.11 ± 49.10%) compared to QF Solution (83.15 ± 9.82%) suggested higher transport of QF from QF:BO ME to rat brain. Overall, it was concluded that BO enhances the brain bioavailability of poorly permeable drugs across the olfactory neuroepithelium, thereby proving its potential in the area of brain drug delivery system.

Nanocrystallization has emerged as a potential solubility enhancement approach for many active pharmaceutical ingredients. Electrospraying has generated a lot of curiosity with its tremendously unexplored potential in the field of pharmaceutical sciences. The present work aims to improve the solubility of Docetaxel by nanocrystallization approach, exploring electrospraying as a novel solidification technique. Electrosprayed nanocrystals were evaluated for wettability, the physical state of drug present, size after re-dispersion, and the % drug release. In vivo studies were also performed in the carcinogen-induced lung cancer model to compare the efficacy of nanocrystals versus unprocessed drug. The results revealed that the drug to stabilizer (Pluronic® F-127) ratio of 1:5, a solvent to the anti-solvent ratio (Ethanol: Water) of 1:10 v/v, and a stirring speed of 600 rpm, led to the formation of drug nanosuspension having the size of 271 ± 19 nm, and PDI of 0.287 ± 0.25 respectively. Upon electrospraying, the size was further increased to 458 ± 57 nm. Results revealed that the drug was present in the crystalline form, even after electrospraying. In-vivo studies conducted in carcinogen-induced lung cancer model showed no significant difference in the number of tumorous nodules formed. However, the developed formulation was more effective in reducing tumor load. Thus, the study concluded that electrospraying could be utilized as one of the potential drying techniques for nano-formulations.

Systemic drug delivery in schizophrenia is a major challenge due to presence of obstacles like, blood-brain barrier and P-glycoprotein, which prohibit entry of drugs into the brain. Quetiapine fumarate (QF), a substrate to P-glycoprotein under goes extensive first pass metabolism leading to limited absorption thus necessitating frequent oral administration. The aim of this study was to develop QF based microemulsion (ME) with and without chitosan (CH) to investigate its potential use in improving the bioavailability and brain targeting efficiency following non-invasive intranasal administration. QF loaded ME and mucoadhesive ME (MME) showed globule size, pH and viscosity in the range of 29-47nm, 5.5-6.5 and 17-40cP respectively. CH-ME with spherical globules having mean size of 35.31±1.71nm, pH value of 5.61±0.16 showed highest ex-vivo nasal diffusion (78.26±3.29%) in 8h with no sign of structural damage upon histopathological examination. Circular plume with an ovality ratio closer to 1.3 for CH-ME depicted ideal spray pattern. Significantly higher brain/blood ratio of CH-ME in comparison to QF-ME and drug solution following intranasal administration revealed prolonged retention of QF at site of action suggesting superiority of CH as permeability enhancer. Following intranasal administration, 2.7 and 3.8 folds higher nasal bioavailability in brain with CH-ME compared to QF-ME and drug solution respectively is indicative of preferential nose to brain transport (80.51±6.46%) bypassing blood-brain barrier. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery.

The objective of the present investigation was to optimize and develop venlafaxine (VLF) loaded nanostructured lipid carrier (NLC) using QbD and risk assessment approach. Full factorial 3 2 design was applied using two independent variables viz ., X1: Drug to total lipid ratio and X2: Surfactant concentration whereby their effect on dependent variables viz ., Y1: Size, Y2: PDI and Y3: %EE was studied. Compritol 888 ATO and Capmul MCM EP showed highest solubility for VLF as solid and liquid lipid respectively which depicted superior miscibility at solid: liquid lipid ratio of 70:30% w/w. VLF NLC were formulated based on optimized formula obtained from design space which gave experimental values for CQA (Size: 77.08 ± 3.45 nm, PDI: 0.234 ± 0.062 and %EE: 81.33 ± 3.05). FTIR, DSC and XRD studies revealed formation of less ordered crystalline structure of lipid matrix favouring higher encapsulation of VLF. Ex-vivo diffusion study showed higher flux value with VLF NLC (14.2 ± 0.40 μg/cm 2 /h) in comparison to VLF solution (9.62 ± 0.59 μg/cm 2 /h) across goat nasal mucosa. VLF NLC did not show toxicity and nasal mucosa was intact indicating safety for intranasal administration. Overall, QbD approach sounds to be apt for the successful development of VLF NLC.

Solid form of drug plays the central role in optimizing its physicochemical properties, thus discovery of new solid forms always provides more options to achieve the desirable pharmaceutical profiles of drugs. Recently, certain drugs have been found to form crystalline inclusion complexes (ICs) with multiple types of linear polymers, representing a new sub-category of pharmaceutical solids. In this study, Finasteride (FNS) was used as the model host and poly (ethylene glycol) (PEG) as the guest, to form ICs of drug with the purpose of offering solubility advantage. Electrospraying as a novel approach was used for production of micro-particles of crystalline ICs of FNS, as it gave narrow particle size distribution and dry powder as end product. The obtained dry powder was characterized using powder X-ray diffraction, NMR spectroscopy and other characterization methods. The results revealed that FNS formed ICs with the biodegradable hydrophilic polymer (PEG), thus offering a FNS-PEG ICs as a potential new solid form. Compared with pure FNS crystals the FNS-PEG ICs crystals showed significantly higher solubility and faster dissolution rates; making it more suitable to achieve higher drug release profiles. Results demonstrated the possibility of using drug-polymer ICs microparticles as solid forms, providing a new approach to design formulations with enhanced drug release. In a nutshell developed formulation was found to be suitable for enhancing water solubility of poorly soluble actives.

Aim of the current study was to evaluate the biodistribution of Butter oil (BO), and Fish oil (FO) loaded Rivastigmine hydrogen tartrate (RHT) microemulsion in blood and brain via intranasal route (IN). For that, binary mixtures of RHT BO and RHT FO (in the ratio of 1:9 to 9:1) were prepared by simple physical mixing and optimized by in-vitro diffusion study. The ratio of a binary mixture which gave higher diffusion of RHT was selected and added in ME for the development of RHT BO ME and RHT FO ME. The developed formulation exhibited lower globule size (65.76 ± 5.23 nm and 69.72 ± 7.85 nm) and PDI (0.180 ± 0.029 and 0.290 ± 0.010) respectively. In-vitro cytotoxicity study revealed safety of formulation for delivery via IN route. Higher bioavailability and Direct Targeting potential value was observed with RHT FO ME and RHT BO ME in comparison to RHT ME via IN route, suggesting that BO and FO enhanced the diffusion of RHT across nasal olfactory membrane to brain.

Recent analysis of the published data reveals the increasing importance of nanotechnology in the field of drug delivery, especially due to easy modulation of drug release and targeting effect. Various conventional methods including nanoprecipitation, spray drying, solvent evaporation, supercritical fluid extraction and ionotropic gelation are well-explored for lab-scale production of nanoparticles and present their own advantages and limitations. Electrospraying a variant of electrospinning is a method based on the processing of polymeric solutions/melt under high electrical voltage to produce particles of desired nature; post optimization of process parameters. This technique is comparatively newer one presenting itself as a competent alternative for the production of polymeric nanoparticles. Owing to its simplicity and flexibility electrospraying can be used to generate particulate material with meticulous structure, size and morphology; providing advantages of controlled release, improved dissolution rate, taste masking of drug candidates and many more. There is very less literature offering pertinent information about the production of nanoparticles by electrospraying technique as most of them deal with materialistic parameters only. This creates a void in learning and understanding of this novel technique for production of nanoparticles encapsulating drug candidates. Also there is a need of exploration in terms of drug release. Present article will provide an overview of electrospraying based production of nanoparticles for controlled and customized drug delivery, to fill this gap. Basic principle, instrumental set-up, advantages and limitations of electrospraying technique over other conventional nanoparticle production techniques and critical process parameters affecting nanoparticle properties is dealt in detail. Brief description of various polymeric nanoparticles (Polymers of natural as well as synthetic origin) with numerous case studies is given providing vast knowledge of drug encapsulation and modulated release patterns in correlation to polymer type used, structure and morphology of nanoparticles produced.

Since the discovery of fatty acids, a niche has been carved for their vital role as adjuvants in drug delivery and as treatment for various diseases. The literature has repeatedly described the essential role of various fatty acids in treating a wide range of diseases and disorders, from central nervous system diseases to wound healing. The use of fatty acids has expanded to many horizons and in recent decades they have gained importance as drug delivery adjuvants in addition to their auxiliary benefits in treating various diseases. Although fatty acids aid in solving both formulation-based and therapeutic challenges to our knowledge, they have never been viewed as dual agents in modern scientific literature. The aim of this review was to provide this perspective and combine the very discreet literature about fatty acids, which includes their role as therapeutic adjuvants and drug delivery agents. It gives insights on the use of fatty acids in treating the diseases of the eye, skin, central nervous system, viral diseases, and so on. The review further discusses how the structure of fatty acids plays an important role in therapeutic activity and affects formulation stability.

In the present work nanocrystal-based formulation of risperidone (RIS) was proposed to overcome solubility issue of RIS, while lyophilization technique was used effectively, for conversion of RIS nanosuspension to solid state.RIS nanosuspension was developed and stabilized with a combination of polycaprolactone and PluronicVarious process parameters affecting average particle size and polydispersity index (PDI), viz. drug to surfactant ratio, solvent to anti-solvent ratio, stirring speed, type of stabilizer were optimized. Assessment of lyophilization as a suitable solidification technique (for conversion to powder form) was done with selective cryoprotectants (trehalose dihydrate and sorbitol).The formulation was found to be stable at 4 °C for 3 months with size, PDI and zeta potential of 214 ± 3.4 nm, 0.120, and -10.2 ± 0.90 mV, respectively. Release profile of developed nanosuspension showed cumulative % release of ∼90% in initial 10 h whereas the value for the unprocessed drug was ∼11% in same time frame.These findings suggest that developed formulation was able to enhance water solubility of the drug effectively and can be potentially used in the management of psychotic disorders.

Advancements in in silico techniques of lead molecule selection have resulted in the failure of around 70% of new chemical entities (NCEs). Some of these molecules are getting rejected at final developmental stage resulting in wastage of money and resources. Unfavourable physicochemical properties affect ADME profile of any efficacious and potent molecule, which may ultimately lead to killing of NCE at final stage. Numerous techniques are being explored including nanocrystals for solubility enhancement purposes. Nanocrystals are the most successful and the ones which had a shorter gap between invention and subsequent commercialization of the first marketed product. Several nanocrystal-based products are commercially available and there is a paradigm shift in using approach from simply being solubility enhancement technique to more novel and specific applications. Some other aspects in relation to parenteral nanosuspensions are concentrations of surfactant to be used, scalability and in vivo fate. At present, there exists a wide gap due to poor understanding of these critical factors, which we have tried to address in this review. This review will focus on parenteral nanosuspensions, covering varied aspects especially stabilizers used, GRAS (Generally Recognized as Safe) status of stabilizers, scalability challenges, issues of physical and chemical stability, solidification techniques to combat stability problems and in vivo fate. KEY WORDS: Parenteral, Nanosuspension, Stabilizer, In vivo fate, Solidification, Scalability

Eye is the unique sense organ with complex and sophisticated anatomy and physiology. Being most instrumental for vision, it is secured by varied protective barriers; ranging from static (membranous) to dynamic (vascular) barrier. Although these barriers are very efficient to protect eye from exogenous substances and external stress, it is caught by various irreversible vision impairing ailments like cataract, conjunctivitis, glaucoma, uveitis, diabetic retinopathy (DR), diabetic macular edema (DME), age related macular degeneration (AMD), cytomegalovirus (CMV) retinitis, retinitis pigmentosa (RP), retinal vein occlusion (RVO), endophthalmitis affecting both anterior and posterior segment of eye. The treatment needed to reach the site of action is restricted by its characteristic barriers. The protective mechanism turns into hurdles when it comes to drug delivery especially in case of posterior segment of eye. Most common and preferable routes for ocular drug delivery are topical and systemic routes owing to their compliance and non-invasive nature, however they turned inefficient in delivering drugs to posterior segment. Currently, other local routes like intraocular and periocular (subconjunctival, subtenon, posterior juxtascleral, retrobulbar, peribulbar) are being explored and are showing positive outcomes in terms of symptomatic relief for a certain time period. But as these are invasive techniques, they also have some hidden long-term drawbacks on other side. Various advancements have been achieved till date in delivery of drug to posterior segment of eye, however despite these advancements; there is need of non-invasive or preferably less invasive technique considering prolonged treatments for such ailments. At times, dependency on invasive techniques may cause problems like patient incompliance, inflammation, contact cataract, retinal detachment, endophthalmitis etc. Here, in this review, barriers in ocular delivery, routes and recent advances in drug delivery to eye including patented commercial formulations with emphasis on posterior segment will be discussed.

The aim of the study was to formulate a microemulsion (ME) using chitosan (CH) and the butter oil (BO) as a permeation enhancer for targeting drug to the posterior segment of the eye, via topical route. Triamcinolone acetonide (TA) was selected as the model drug since it undergoes extensive first-pass metabolism, leading to poor oral bioavailability of 23%. For optimisation of BO concentration, different ratios of TA:BO were prepared by simple physical mixing in the ratio of 1:9 to 9:1 and diffusion study was performed. MEs containing TA, TA:BO and TA CH ME were formulated by water titration method. Globule sizes of TA ME, TA:BO ME and TA CH ME were found to be 66.06 ± 0.32 nm, 78.52 ± 1.50 nm and 97.30 ± 2.50 nm, respectively. In ex vivo diffusion studies using goats eye, TA:BO ME (31.33 ± 0.46 and 33.98 ± 0.23) and TA CH ME (24.10 ± 0.41 and 27.00 ± 0.18) showed higher percentage of drug diffusion in comparison to TA ME (13.29 ± 0.41and 15.56 ± 0.34) and TA solution (8.20 ± 1.04 and 10.39 ± 0.22) in presence and in absence of vitreous humour. Fluorescence intensity of coumarin-6 (as a marker) loaded ME with BO and CH was found to be higher, confirming their role in altering membrane permeability and facilitating coumarin-6 diffusion to the posterior chamber. Overall, it was concluded that BO enhances the bioavailability of TA across the retina, thereby proving its potential as permeation enhancer in facilitating drug delivery to the posterior segment of the eye.