Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus.

In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer's results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.

Beneficial effect of aspirin against interferon-α-2b-induced depressive behavior in Sprague Dawley rats.

Accumulating data advocates that inflammatory mediators may contribute to depression in experimental models as well as in humans. Nonetheless, whether anti-inflammatory treatments can prevent depression still remains controversial. To substantiate our hypothesis, we used an interferon-α-2b model of depression using Sprague Dawley rats. Interferon-α-2b is a cytokine which activates immune response and also produces depression. The animals were treated for 21 days with aspirin (10 mg/kg, per oral (p.o.)) dexamethasone (1 mg/kg p.o.) and amitriptyline (10 mg/kg p.o.). Amitriptyline was used as reference standard, and given concurrently with aspirin and dexamethasone to examine any synergy. Interferon-α-2b (6000 IU/kg, intraperitoneal (i.p.)) was administered in all the above groups daily, except normal control. Tests performed included sucrose preference test, behavioural tests like forced swim test, elevated plus maze, light dark box and locomotor activity along with biochemical estimations like serum cortisol and brain neurotransmitters. The rats in the group treated with Interferon-α-2b produced depressive behaviour in rats. We found that animals treated with aspirin decreased immobility time in forced swim test, increased sucrose preference, decreased serum cortisol and increased brain serotonin levels signifying antidepressant action. In contrast, there was no effect in groups treated with dexamethasone. Our results suggest that aspirin can serve as a potential antidepressant both individually and as adjuvant agent in the treatment of depression. Inhibition of the cyclo-oxygenase-2 levels and prostaglandins concentration or any other potential physiological and biochemical mechanisms may be involved in antidepressant effect.

An Overview of Metallic Nanoparticles: Classification, Synthesis, Applications, and their Patents.

BACKGROUND: Nanotechnology has gained enormous attention in pharmaceutical research. Nanotechnology is used in the development of nanoparticles with sizes ranging from 1-100nm, with several extraordinary features. Metallic nanoparticles (MNPs) are used in various areas, such as molecular biology, biosensors, bio imaging, biomedical devices, diagnosis, pharmaceuticals, etc., for their specific applications. METHODOLOGY: For this study, we have performed a systematic search and screening of the literature and identified the articles and patents focusing on various physical, chemical, and biological methods for the synthesis of metal nanoparticles and their pharmaceutical applications. RESULTS: A total of 174 references have been included in this present review, of which 23 references for recent patents were included. Then, 29 papers were shortlisted to describe the advantages, disadvantages, and physical and chemical methods for their synthesis, and 28 articles were selected to provide the data for biological methods for the formulation of metal NPs from bacteria, algae, fungi, and plants with their extensive synthetic procedures. Moreover, 27 articles outlined various clinical applications of metal NPs due to their antimicrobial and anticancer activities and their use in drug delivery. CONCLUSION: Several reviews are available on the synthesis of metal nanoparticles and their pharmaceutical applications. However, this review provides updated research data along with the various methods employed for their development. It also summarizes their various advantages and clinical applications (anticancer, antimicrobial drug delivery, and many others) for various phytoconstituents. The overview of earlier patents by several scientists in the arena of metallic nanoparticle preparation and formulation is also presented. This review will be helpful in increasing the current knowledge and will also inspire to innovation of nanoparticles for the precise and targeted delivery of phytoconstituents for the treatment of several diseases.

Deciphering the Therapeutic Applications of Nanomedicine in Ovarian Cancer Therapy: An Overview.

The majority of deadly cancers that afflict the female reproductive system occur in the ovary. Around 1,40,000 women worldwide die from ovarian cancer each year, making it the sixth most common cancer-associated deceases among females in the United States. Modern, cutting-edge treatments like chemotherapy and surgery frequently produce full remissions, but the recurrence rate is still very high. When this crippling condition is diagnosed, there are frequently few therapeutic choices available because of how quietly it manifests. Healthcare practitioners must have a fundamental grasp of the warning signs and symptoms of ovarian cancer, as well as the imaging techniques and treatment choices available, to give the patient the best care possible. The discipline of medical nanotechnology has gained a lot of momentum in recent years in resolving issues and enhancing the detection and treatment of different illnesses, including cancer. This article gives a brief summary of types, risk factors and approaches to ovarian cancer treatment. We subsequently discussed the pathophysiology of ovarian cancer with the risk factors. This review also emphasizes the various signalling pathways involved in ovarian cancer. Our comprehensive integration of recent findings in fundamental research in the nano arena reveals the strong interest in these nanomedicines in ovarian cancer treatment. However, these nanomedicines still require more research, as indicated by the comparatively small number of clinical trials ongoing. This article will provide a reference for ovarian cancer treatment.

Emerging Treatment Options of Pluronic in Designing Colloidal Nano and Microcarriers Carriers for Various Therapies.

Poloxamers, commonly known as Pluronics, are a special family of synthetic tri-block copolymers with a core structure made of hydrophobic poly (propylene oxide) chains sandwiched by two hydrophilic poly (ethylene oxide) chains. It is possible to modify the mechanical, bioactive, and microstructural characteristics of Pluronics to simulate the behavior of different types of tissues. Additionally, they are auspicious drug carriers with the capacity to increase therapeutic agent availability and to design nano-drug formulations for various ailments. The nanoformulation composed of Pluronics is more susceptible to cancer cells due to their amphiphilic nature and feature of selfassembling into micelles. Today's expanding poloxamer research is creating new hopes that increase the possibility of new remedies for a brand-new nanomedicine age treatment. This article provides a concise overview of the classification, grading, and attributes of drug delivery systems (DDSs) as well as the potential for Pluronics to create micro and nanocarriers. We subsequently discuss its utility in drug delivery for cancer, gene therapy, anti-infective therapy, antioxidants, anti-diabetic drugs, anti-HIV, Alzheimer's disease, and antimicrobial drugs. This review also highlighted several patented formulations that contain various grades of Pluronics in one or more different ways. The recent findings in fundamental research in the field properly demonstrate the strong interest in these novel pharmaceutical strategies.

Untangling breast cancer: Trailing towards nanoformulations-based drug development.

All over the world, cancer death and prevalence are increasing. Breast cancer (BC) is the major cause of cancer mortality (15%) which makes it the most common cancer in women. BC is defined as the furious progression and quick division of breast cells. Novel nanotechnology-based approaches helped in improving survival rate, metastatic BC is still facing obstacles to treat with an expected overall 23% survival rate. This paper represents epidemiology, classification (non-invasive, invasive and metastatic), risk factors (genetic and non-genetic) and treatment challenges of breast cancer in brief. This review paper focus on the importance of nanotechnology-based nanoformulations for treatment of BC. This review aims to deliver elementary insight and understanding of the novel nanoformulations in BC treatment and to explain to the readers for enduring designing novel nanomedicine. Later, we elaborate on several types of nanoformulations used in tumor therapeutics such as liposomes, dendrimers, polymeric nanomaterials and many others. Potential research opportunities for clinical application and current challenges related to nanoformulations utility for the treatment of BC are also highlighted in this review. The role of artificial intelligence is elaborated in detail. We also confer the existing challenges and perspectives of nanoformulations in effective tumor management, with emphasis on the various patented nanoformulations approved or progression of clinical trials retrieved from various search engines.

Self-Assembly Polymeric Nano Micelles for the Futuristic Treatment of Skin Cancer and Phototoxicity: Therapeutic and Clinical Advancement.

In the last few years, the polymeric micelles played a major role as a drug carrier in nano-sized drug delivery system. The polymeric micelles are designed from synthetic block co-polymers and graft copolymers. In the mixed micelles, the bilayer lipid membrane and surfactants are used. Both micelles are in nano-sized and used to enhance the drug delivery to treat different diseases. In this review, we will discuss some examples from the literature included demonstrating the polymeric micelles used as drug-carriers in skin cancer treatment by using different drugs. We also summarized mixed micelles, polymeric micelles in skin drug delivery, various polymers, and techniques of polymeric micelles. These micelles may improve delivery of drug in the skin's targeted sites in specific and dermatological diseases like skin cancer, acne, and fungal infection. In the comparison of surfactant micelles, the polymeric micelles are more stable. Polymeric micelles act as a colloidal carrier for incorporating poorly water-soluble and amphiphilic drugs.

QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310-3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

Insights on Development Aspects of Polymeric Nanocarriers: The Translation from Bench to Clinic.

Scientists are focusing immense attention on polymeric nanocarriers as a prominent delivery vehicle for several biomedical applications including diagnosis of diseases, delivery of therapeutic agents, peptides, proteins, genes, siRNA, and vaccines due to their exciting physicochemical characteristics which circumvent degradation of unstable drugs, reduce toxic side effects through controlled release, and improve bioavailability. Polymers-based nanocarriers offer numerous benefits for in vivo drug delivery such as biocompatibility, biodegradability, non-immunogenicity, active drug targeting via surface modification, and controlled release due to their pH-and thermosensitive characteristics. Despite their potential for medicinal use, regulatory approval has been achieved for just a few. In this review, we discuss the historical development of polymers starting from their initial design to their evolution as nanocarriers for therapeutic delivery of drugs, peptides, and genes. The review article also expresses the applications of polymeric nanocarriers in the pharmaceutical and medical industry with a special emphasis on oral, ocular, parenteral, and topical application of drugs, peptides, and genes over the last two decades. The review further examines the practical, regulatory, and clinical considerations of the polymeric nanocarriers, their safety issues, and directinos for future research.

Itraconazole loaded nano-structured lipid carrier for topical ocular delivery: Optimization and evaluation.

BACKGROUND & OBJECTIVES: Low penetration efficiency and retention time are the main therapeutic concerns that make it difficult for most of the drugs to be delivered to the intraocular tissues. These challenging issues are often related to those drugs, which have low or poor solubility and low permeability. The goal of this study was designed to develop nanostructured lipid carriers (NLCs) loaded with itraconazole (ITZ) with the objective of enhancing topical ocular permeation and thereby improving clinical efficacy. MATERIALS AND METHODS: ITZ-loaded NLCs were fabricated by a high-speed homogenization technique using surfactant (Poloxamer 407), and lipids (stearic acid and oleic acid). Optimization of formulations was performed by 3 level factorial design and the selected formulation (F6) was evaluated by differential scanning calorimetry and transmission electron microscopy. Antifungal activity was assessed by measuring the zone of inhibition and irritation potential using the HET-CAM test. RESULTS: The independent variables (lipid ratio-X1 and percentage of emulsifier-X2) have a positive impact on percentage entrapment efficiency (Y2) and percentage release (Y3) but have a negative impact on particle size (Y1). Based on the better entrapment efficiency (94.65%), optimum particle size (150.67 nm), and percentage cumulative drug release (68.67%), batch F6 was selected for further evaluation. Electron microscopic images revealed that the prepared particles are spherical and have nano size. Antifungal studies demonstrated enhancement in the zone of inhibition by formulation F6 as compared to a commercial eye drop. The non-irritancy of optimized formulation (F6) was confirmed with a zero score. INTERPRETATION & CONCLUSION: In summary, the optimized NLCs seem to be a potent carrier for the effective delivery of itraconazole in ocular therapy.

Formulation Development and Evaluation of Novel Vesicular Carrier for Enhancement of Bioavailability of Poorly Soluble Drug.

BACKGROUND: Niosomes are a vesicular carrier system comprised of a Nonionic surfactant bilayer surrounding an aqueous compartment. Niosomes are presumed to raise the intake of the poorly water-soluble drugs by M cells of Peyer's patches present in the intestine's lymphatic tissues, thereby avoiding the first-pass metabolism and increasing its oral bioavailability. Biodegradability, nonimmunogenic nature, minimal side effects, low cost, good stability, and flexibility to incorporate hydrophilic and lipophilic drugs are other advantages of niosomes. OBJECTIVE: To formulate and evaluate a novel vesicular carrier system of a poorly soluble drug Lurasidone hydrochloride for the enhancement of its solubility and bioavailability. METHODS: The thin-film hydration technique used to prepare Lurasidone hydrochloride loaded niosomes using different grades of nonionic surfactants like Brij, Span, and Tween. They evaluated for particle size, zeta potential, percent entrapment efficiency, in-vitro drug release, and in-vivo study. RESULTS: Niosomes comprised of Brij S-100 in drug: cholesterol: surfactant (1:1:1) showed particle size (1.15 ± 0.21 µm) and percent entrapment efficiency (97.02 ± 0.21%) and was selected for further studies. Various pharmacokinetic parameters like Cmax (281.27ng/ml), Tmax (5 h), and AUC (2640.197) were found to be significantly improved compared to plain drug solution. CONCLUSION: The Niosomal formulation could be the promising drug delivery system for the controlled and sustained release of Lurasidone.

Pharmacokinetics and Pharmacodynamics of Curcumin-Loaded Solid Lipid Nanoparticles in the Management of Streptozotocin-Induced Diabetes Mellitus: Application of Central Composite Design.

Due to poor bioavailability and chemical instability, the effectiveness of curcumin is negligible in the treatment of numerous diseases. Solid lipid nanoparticles (SLNs) increase the bioavailability of lipophilic compounds and protect the drug from gastrointestinal degradation. The objective of our study is the utilization of SLNs to improve the pharmacokinetics and pharmacodynamics of curcumin in the management of diabetes mellitus. Central composite design was used to prepare curcumin-loaded SLNs (Cur-SLN). The analysis of independent variables like drug concentration, lipid concentration, and surfactant concentration was carried out using analysis of variance (ANOVA) to obtain the optimized batch (optimized Cur-SLN) having the desired values of dependent variables particle size and entrapment efficiency. In vitro release, differential scanning calorimeter (DSC), transmission electron microscopy (TEM), and Fourier Transform Infra-Red (FTIR) studies of optimized Cur-SLN were carried out and then its pharmacokinetic and pharmacodynamic studies were performed. The model was found to be significant for particle size and entrapment efficiency based on F-value and p-value. The optimized batch's predicted values were in close agreement with the actual values of particle size and entrapment efficiency. TEM results confirm mono-dispersion and spherical shape of particles in the formulation. The DSC results confirmed the changing of drug from crystalline to amorphous form. Burst release followed by the sustained release was obtained in the in vitro release studies. The pharmacokinetic study shows enhanced bioavailability of optimized Cur-SLN compared with a plain drug suspension. The optimized Cur-SLN achieved higher antidiabetic activity in streptozotocin-induced diabetes mellitus rats than the plain drug suspension. SLNs can be used as a promising technique for delivering curcumin in the management of diabetes mellitus.

Design and Optimization of Febuxostat-loaded Nano Lipid Carriers Using Full Factorial Design.

OBJECTIVES: This work aims to develop nanostructured lipid carriers (NLCs) to improve the oral bioavailability of febuxostat (FEB). MATERIALS AND METHODS: High shear homogenization, a well-known technique, followed by bath sonication with slight modifications was used to prepare FEB-loaded NLCs using oleic acid as liquid lipid and stearic acid as solid lipid. A total of 3² full factorial design was utilized to examine the effect of 2 independent variables, namely, X1 (liquid to solid lipid ratio) and X2 (surfactant concentration) on the Y1 (particle size) and Y2 (% entrapment efficiency) of the drug. The prepared NLCs were evaluated for particle size, polydispersity index, zeta potential, and (%) entrapment efficiency. RESULTS: The drug's highest solubility was found in the stearic (solid lipid) and oleic acid (liquid lipid), which were further chosen for NLC preparation. Result of the present study showed an increase in entrapment efficiency and a decrease in particle size with the increase in liquid lipid to solid lipid ratio. With increased surfactant concentration, a small particle size is observed. The optimized formulation's particle size and (%) entrapment efficiency was found to be 99 nm and 80%, respectively. The formulations' zeta potential and polydispersity index were found within the range. Compared to plain drug suspension, the optimized formulation showed higher drug release, which may be due to the presence of the higher amount of liquid lipid. The particles shown in the transmission electron microscopy were round in shape and have smooth surface. Stability studies showed that the NLC formulation can be stored for a longer time period under room condition. CONCLUSION: FEB-loaded NLC were successfully prepared using full 3² factorial design, and can be further used for oral delivery of FEB for gout treatment.

A Current Review on Drug Loaded Nanofibers: Interesting and Valuable Platform for Skin Cancer Treatment.

BACKGROUND: Nanofibers are used in topical medication for various skin diseases like wound healing, skin cancer and others. Non-melanoma skin cancers (NMSCs) are the most widely distributed diseases in the world, of which 99% of people are affected by either basal cell carcinomas (BCCs) or squamous cell carcinomas (SCCs) of the skin. Skin malignancy is caused by direct sun exposure and regular application of unsafe restorative items on the skin. OBJECTIVE: This review presents the use of nanofibers in skin cancer treatment and advances made in skin cancer treatment. METHODS: There are various methods used in the production of nanofibers such as bicomponent extrusion, phase separation, template synthesis, drawing, electrospinning, and others. Electrospinning is the most widely used technique for nanofiber fabrication. The nanofibers are produced in nanometer size range and mostly used in medication because of their low thickness, large surface area per unit mass and porosity. Nanofibers are also used as drug delivery system for sustaining the action of drugs or medicaments. RESULTS: Nanofibers enhance the permeation and availability of those drugs having low bioavailability and low permeability. Nanofibers increase the sustainability of the drugs up to 10 days. CONCLUSION: Skin cancer is the abnormal growth of skin cells in the body influencing people of all colours and skin. In this review paper, the definition and production techniques of nanofibers and drugs used in skin cancer treatment and the relation between skin cancer and nanofiber are illustrated in detail. With the help of different techniques and drugs, the risk of non-melanoma skin cancer is reduced. Lay Summary: The risk of skin cancer and other skin problems is increasing day by day. In a previous study we found that the nanofibers are less used as a topical delivery system. We have studied the nanofibers as a drug delivery system in the treatment of skin cancer by using different drugs. According our study nanofibers are most useful in skin drug delivery and if the nanofiber, are merging with other drug delivery system like nanoparticles, it may maximize the output of drug into skin. The significance of this study is, to explain all information about nanofibers in skin cancer.

Method Development and Validation of UV Spectrophotometric Method for the Quantitative Estimation of Curcumin in Simulated Nasal Fluid.

BACKGROUND: Curcumin is a polyphenolic compound with numerous therapeutic activities. There is no validated method available for the quantitative estimation of curcumin in simulated nasal fluid. OBJECTIVE: The aim of present investigation was to develop a simple and precise UV visible spectrophotometric method for estimation of pure form of curcumin in simulated nasal fluid. METHOD: Suitable solvent system was selected by estimation of curcumin at UV maxima of 421nm in simulated nasal fluid with two surfactants (tween 80 and sodium lauryl sulphate). The double beam UV visible spectrophotometer was used for measurement of absorption. The selected solvent system was further validated according to guidelines of international conference on harmonization (ICH), the analytical parameter like linearity, precision and accuracy etc. were studied. RESULTS: Simulated nasal fluid with tween 80 at 1% concentration satisfied all the conditions relative to Peak quality at the stated wavelength. In developed method, curcumin was found to be linear over selected concentration range of 5 to 60µg/ml with a correlation coefficient of 0.998. The accuracy was found to be in range of 99.51 -100.223%.The precision was found to be less than 2 in terms of % RSD. The LOD & LOQ were 0.3657 & 1.109 respectively. CONCLUSION: The proposed method was found to be simple, sensitive and precise. The most important this method can be used for routine quality control analysis of curcumin with accuracy.

Development and Validation of In Vitro Discriminatory Dissolution Testing Method for Fast Dispersible Tablets of BCS Class II Drug.

OBJECTIVES: Fast dispersible tablets (FDTs) get dispersed very fast due to which the discrimination of in vitro drug release and their evaluation is difficult. Hence in the present study a new in vitro discriminatory dissolution method was developed and validated for FDTs of domperidone of BCS class II. MATERIALS AND METHODS: FDTs of domperidone were prepared by direct compression method. The dissolution studies were performed in an eight-station Electrolab TDT-082 dissolution testing apparatus, analyzed by ultraviolet spectrophotometer and evaluated in different dissolution mediums i.e. sodium lauryl sulphate (0.5%, 1.0% and 1.5%) with fresh distilled water, simulated intestinal fluid pH 6.8, simulated gastric fluid pH 1.2 without enzymes, phosphate buffer solution (pH 6.8) and 0.1 N hydrochloric acid at different agitation speeds. RESULTS: The developed method was validated in terms of specificity, accuracy, precision, linearity and robustness. Amongst the different mediums, 0.5% sodium lauryl sulfate (SLS) with distilled water was found to be optimum with higher rate of discriminatory power. The percentage recovery was found to be 96 to 100.12 % and the % relative standard deviation value for precision (intraday and interday) was found to be less than 1%. Also a dissolution profile of prepared FDTs were compared in distilled water containing 0.5% SLS using similarity (f2) and dissimilarity (f1) factor calculation which showed dissimilarity in release profile and confirms the discriminatory nature of developed method. CONCLUSION: The discriminatory dissolution method for FDTs was developed and validated. All the obtained results were satisfactory, accurate and in range. The current method could be beneficial for formulation development and for assessment of quality of FDTs.

Intranasal Lipid Particulate Drug Delivery Systems: An Update on Clinical Challenges and Biodistribution Studies of Cerebroactive Drugs in Alzheimer's disease.

BACKGROUND: Alzheimer's is the primary cause of death in the various countries that affect wide strata of the population. The treatment of it is restricted to a few conventional oral medications that act only superficially. It is evident that the delivery of a drug to the brain across the blood-brain barrier is challenging as the BBB is armed with several efflux transporters like the P-glycoprotein as well as nasal mucociliary clearance adds up leading to decreased concentration and reduced therapeutic efficacy. Considering these, the intranasal IN route of drug administration is emerging as an alternative route for the systemic delivery of a drug to the brain. The intranasal (IN) administration of lipid nanoparticles loaded with cerebroactive drugs showed promise in treating various neurodegenerative diseases, since the nasal route allows the direct nose to brain delivery by means of solid lipid nanoparticles (SLN's). The tailoring of intranasal lipid particulate drug delivery systems is a pleasing approach to facilitate uptake of therapeutic agents at the desired site of action, particularly when a free drug has poor pharmacokinetics/ biodistribution (PK/BD) or significant off-site toxicities. OBJECTIVES: 1) In this review, key challenges and physiological mechanisms regulating intranasal brain delivery in Alzheimer's disease, ex vivo studies, pharmacokinetics parameters including brain uptake and histopathological studies are thoroughly discussed. 2) A thorough understanding of the in vivo behaviour of the intranasal drug carriers will be the elusive goal. 3) The article emphasizes to drag the attention of the research community working in the intranasal field towards the challenges and hurdles of the practical applicability of intranasal delivery of cerebroactive drugs. METHOD: Various electronic databases, journals like nanotechnology and nanoscience, dove press are reviewed for the collection and compilation of data. RESULTS: From in vivo biodistribution studies, pharmacokinetics parameters, and gamma scintigraphy images of various drugs, it is speculated that intranasal lipid particulates drug delivery system shows better brain targeting efficiency for various CNS disorders in comparison to other routes. CONCLUSION: Various routes are explored for the delivery of drugs to increase bioavailability in the brain for CNS disorders but the intranasal route shows better results that pave the way for success in the future if properly explored.

A Novel Approach of Drug Localization through Development of Polymeric Micellar System Containing Azelastine HCl for Ocular Delivery.

BACKGROUND: Development of polymeric micelles for the management of allergic conjunctivitis to overcome the limitations of topical installation, such as poor patient compliance, poor stromal permeability, and significant adverse effects, increase precorneal residence time and efficacy, and also control the release of drug at the target site. OBJECTIVE: The investigation was aimed at developing a polymeric micellar system of Azelastine HCl for Ocular Delivery. METHODS: Drug loaded micelles of tri-block copolymers Pf 127 were prepared by Thin Film hydration method. The polymeric micelles formulations (F1 to F9) were assessed for entrapment efficiency, micelle size, in vitro permeation, ex vivo transcorneal permeation, in vivo Ocular Irritation, and Histology. RESULTS: Optimized micelles formulation (F3), with the lowest micelle size of 92 nm, least polydispersity value of 0.135, highest entrapment efficiency of 95.30 ± 0.17%, and a cumulative drug permeation of 84.12 ± 1.26% in 8h, was selected to develop pH-sensitive micelles loaded carbopol in situ gel. The optimized in situ gel (G4) proved to be superior in its ex vivo transcorneal permeation when compared with Market Preparation and pure drug suspension, exhibiting 43.35 ± 1.48% Permeation with zero-order kinetics (r2 = 0.9944) across goat cornea. Transmission Electron microscopy revealed spherical polymeric micelles trapped in the gel matrix. A series of experiments showed hydration capability, non-irritancy, and histologically safe gel formulation that had appropriate handling characteristics. CONCLUSION: A controlled release pH-sensitive ocular formulation capable of carrying the drug to the anterior section of the eye via topical delivery was successfully developed for the treatment of allergic conjunctivitis.

Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis.

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.

Surface Solid Dispersion and Solid Dispersion of Meloxicam: Comparison and Product Development.

Purpose: A comparative study was carried out between surface solid dispersion (SSD) and solid dispersion (SD) of meloxicam (MLX) to assess the solubility and dissolution enhancement approach and thereafter develop as patient friendly orodispersible tablet. Methods: Crospovidone (CPV), a hydrophilic carrier was selected for SSD preparation on the basis of 89% in- vitro MLX adsorption, 19% hydration capacity and high swelling index. SD on the other hand was made with PEG4000. Both were prepared by co-grinding and solvent evaporation method using drug: carrier ratios of 1:1, 1:4, and 1:8. Formulation SSDS3 (MLX: CPV in 1:8 ratio) made by solvent evaporation method showed t50% of 28 min and 80.9% DE50min which was higher in comparison to the corresponding solid dispersion, SDS3 (t50% of 35min and 76.4% DE50min). Both SSDS3 and SDS3 were developed as orodispersible tablets and evaluated. Results: Tablet formulation F3 made with SSD3 with a disintegration time of 11 secs, by wetting time= 6 sec, high water absorption of 78%by wt and cumulative drug release of 97% proved to be superior than the tablet made with SD3. Conclusion: Conclusively, the SSD of meloxicam has the potential to be developed as fast acing formulation that can ensure almost complete release of drug.