Comprehending the potential of metallic, lipid, and polymer-based nanocarriers for treatment and management of depression.

The World Health Organization (WHO) ranked depression as the third leading cause of global burden of disease in 2004, and it is predicted to overtake it and move to first place by 2030. It is a mental disorder that causes significant changes in the mood and day-to-day activity of an individual. Various approaches already exist for treating depression but, none of them are completely successful in treating depression. At present, discovering a new medication or delivery mechanism that can manage depression safely and efficiently is a huge challenge. Conventional formulations used in the management of depression have drawbacks like limited penetration, frequent dosing, toxicity, patient compliance concerns as well as brain barriers which are a big hurdle for antidepressant drugs to reach the brain through conventional formulations. Nano-based formulations are gaining popularity as one of the possibilities to overcome the limitations of conventional formulations by reducing the dose and dosing frequency, increasing the efficacy as well as proving it to be safe and effective means of treating depression. This review targets the neurochemistry and pathophysiological concerns of depression, strategies and problems of conventional therapies, and also recent advances in the metallic, lipid, and polymer-based nanoformulations for a variety of antidepressants. A detailed discussion of the expediency of various nanoformulations like liposomes, nanostructured lipid carriers, solid lipid nanoparticles, ethosomes, nanocapsules, dendrimer, gold and silver nanoparticles are addressed in the current review. In essence, nanoformulations hold great promises for the treatment of depression as they provide a platform with high penetration potential, targeted transmission, and improved protection and efficacy.

Polyethylene oxide and its controlled release properties in hydrophilic matrix tablets for oral administration.

Polymers are excipients that modify the rate of drug release from pharmaceutical dosage forms. Hydrophilic polymer-based controlled drug delivery system is more advantageous as compared to the conventional delivery system as it reduces the dosing frequency, improves therapeutic efficacy, reduces side-effects, and probably enhances patient compliance. Polyethylene oxide (PEO), a nonionic hydrophilic polymer, is one of the most widely used polymers for extending the drug release. This review mainly focuses on the PEO marketed by, but not limited to, The Dow Chemical Company under the trade name of POLYOXTM. It is commercially available polyethylene oxide polymer existing in various molecular weight and viscosity grades depending upon the application. This study essentially discusses chemistry, physicochemical properties, and the impact of formulation and processing variables on the release of drug from hydrophilic PEO matrix tablets. Moreover, it also summarizes the stability, patents, and regulatory perspectives of POLYOX that can further influence the future developments of controlled release dosage forms.

Brain targeted delivery of lurasidone HCl via nasal administration of mucoadhesive nanoemulsion formulation for the potential management of schizophrenia.

This investigation aimed to design, develop, and optimize intranasal nanoemulsion for brain targeted delivery of lurasidone hydrochloride for the management and treatment of schizophrenia. The design of experiment supported optimization of high-pressure homogenization (HPH) process was executed for the manufacturing of lurasidone loaded nanoemulsion. The nanoemulsion comprising of lurasidone hydrochloride (10 mg/mL), 20% Oilmix, 25% surfactant and, 55% aqueous phase (w/w) was processed with HPH at optimized conditions to get droplet size in the nano range. The droplet size of optimized nanoemulsion was found to be 48.07 ± 3.29 nm with a polydispersity index of 0.31 ± 0.01. The optimized translucent nanoemulsion (% transmittance of 88.56 ± 2.47) was found to be non-toxic to sheep nasal mucosa and stable for six months. The results of ex vivo diffusion study revealed the improvement in drug diffused by mucoadhesive nanoemulsion (MLNE) (1.41 × 10-4 ± 1.11 × 10-5 cm2/min) as compared to the solution (1.15 × 10-4 ± 1.35 × 10-5 cm2/min). The results of pharmacodynamic studies in mice uncover the highest inhibition of compulsive behavior (64.63%) and spontaneous locomotor activity (60.87%) shown by MLNE. This may be due to increased bioavailability in a brain, and possibly confirms the potential of nanoemulsion in targeting the brain through nasal route in the treatment of schizophrenia.

Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and Roxithromycin Using a DoE Approach.

The aim of this work was to develop and optimize a robust HPLC method for the separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing Design of Experiment (DoE) approach. The Plackett-Burman design was used to assess the impact of independent variables (concentration of organic phase, mobile phase pH, flow rate and column temperature) on peak resolution, USP tailing and number of plates. A central composite design was utilized to evaluate the main, interaction, and quadratic effects of independent variables on the selected dependent variables. The optimized HPLC method was validated based on ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride and roxithromycin in tablet formulations. The findings showed that DoE approach could be effectively applied to optimize a robust HPLC method for quantification of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical comparison between results of proposed and reported HPLC method revealed no significant difference; indicating the ability of proposed HPLC method for analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical formulations.

Recent Survey on Patents of Nanoemulsions.

BACKGROUND: Colloidal systems are most prominent delivery systems mainly used as vehicles for the transportation, targeting the various types of biomolecules, proteins, peptides, synthetic medicinal agents. OBJECTIVE: To provide concise information on patents that are directly or indirectly related to the nanoemulsions. METHODS: The ample of research work going on with such system, in which small insoluble particle/droplets are dispersed within the immiscible secondary liquid referred to as continuous phase, is enormous. A highly praised colloidal system is nanoemulsion which possesses 'nano' sized droplets of one phase dispersed within second continuous phase. RESULTS: The characteristic features of nanoemulsion are their optical clarity, clear or bluish tint appearance and small globule size (20-200 nm) which makes them insensitive to gravitational instability, dilution and temperature. Above of all, achieving said properties using lower surfactant concentration and by supplying external energy differentiate them from microemulsion, which uses higher amount of surfactant thereby making them toxic for human body. Due to such variable advantages, researchers are engaged in going for the protecting their ideas in nanoemulsions by filling various patents. CONCLUSION: Patents in this review, covers various areas (types of drug delivery and applications) where nanoemulsion are used. Literature revealed that filing of patents on nanoemulsion increased tremendously during last 5 years and will increase in upcoming time as 21st century will be called as the century of nanomedicine.

Evaluation of brain targeting efficiency of intranasal microemulsion containing olanzapine: pharmacodynamic and pharmacokinetic consideration.

The objective of this study was to develop and evaluate olanzapine (OZP) -loaded microemulsions (OZPME) for intranasal delivery in the treatment of schizophrenia. The OZPME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine - induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with technetium-99 ((99m)Tc), and biodistribution of drug in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging in rabbits was performed to determine the uptake of the OZP into the brain. OZPME were found clear and stable with average globule size of 23.87 ± 1.07 nm. In pharmacodynamic assessments, significant (p < 0.05) difference in parameters estimated were found between the treated and control groups. (99m)Tc-labeled OZP solution (OZPS)/OZPME/OZP mucoadhesive microemulsion (OZPMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of OZPMME compared to intravenous OZPME was found to be five to six times higher signifying larger extent of distribution of the OZP in brain. Drug targeting efficiency and direct drug transport were found to be highest for intranasal OZPMME, compared to intravenous OZPME. Furthermore, rabbit brain scintigraphy also demonstrated higher intranasal uptake of the OZP into the brain. This investigation demonstrates a prompt and larger extent of transport of OZP into the brain through intranasal OZPMME, which may prove beneficial for treatment of schizophrenia.

Paliperidone microemulsion for nose-to-brain targeted drug delivery system: pharmacodynamic and pharmacokinetic evaluation.

OBJECTIVE: The objective of present study was to develop and evaluate paliperidone (PALI) loaded microemulsion (PALI-ME) for intranasal delivery in the treatment of schizophrenia. MATERIAL AND METHODS: The PALI-ME was formulated by the spontaneous microemulsification method and characterized for physicochemical parameters. Pharmacodynamic assessments (apomorphine-induced compulsive behavior and spontaneous motor activity) were performed using mice. All formulations were tagged with (99m)Tc (technetium). Pharmacokinetic evaluation of PALI in the brain was investigated using Swiss albino rats. Brain scintigraphy imaging was performed in rabbits. RESULTS AND DISCUSSION: PALI-ME was found stable with average droplet size of 20.01 ± 1.28 nm. In pharmacodynamic studies, significant (p < 0.05) deference in parameters estimated, were found between the treated and control groups. (99m)Tc-tagged PALI solution (PALI-SOL)/PALI-ME/PALI muco-adhesive ME (PALI-MME) was found to be stable and suitable for in vivo studies. Brain-to-blood ratio at all sampling points up to 8 h following intranasal administration of PALI-MME compared to intravenous PALI-ME was found to be 6-8 times higher signifying greater extent of distribution of the PALI in brain. Rabbit brain scintigraphy demonstrated higher intranasal uptake of the PALI into the brain. CONCLUSION: This investigation demonstrates a prompt and larger extent of transport of PALI into the brain through intranasal PALI-MME, which may prove beneficial for treatment of schizophrenia.

Investigating effect of microemulsion components: In vitro permeation of ketoconazole.

The purpose of this study was to evaluate the effect of oil, surfactant/co-surfactant mixing ratios and water on the in vitro permeation of ketoconazole (KTZ) applied in O/W microemulsion vehicle through intact rat skin. Lauryl Alcohol (LA) was screened as the oil phase of microemulsions, due to a good solubilizing capacity of the microemulsion system. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant (S) and ethanol (EtOH) as the cosurfactant (CoS). The formulation which showed a highest permeation rate of 54.65 ± 1.72 µg/cm(2)/h(1) and appropriate physico-chemical properties was optimized as containing 2% KTZ, 10% LA, 20% Lab/EtOH (1:1) and 68% double distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of KTZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of KTZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to KTZ reference. The studied microemulsion formulation showed a good stability for a period of three months. Histopathological investigation of rat skin revealed the safety of microemulsion formulations for topical use. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of KTZ.

Improving the isotretinoin photostability by incorporating in microemulsion matrix.

The present paper demonstrates the increased photostability of isotretinoin when loaded in microemulsion. The photodegradation of isotretinoin, in methanol and microemulsion formulation was studied under direct sun light. The photodegradation process was monitored by UV spectrophotometry. In methanol solution, isotretinoin undergoes complete photodegradation just within a few minutes of light exposure. Isotretinoin incorporated in microemulsion formulation showed an increased stability in comparison to the methanol solutions. In particular for isotretinoin, a residual concentration of 75% was still present after a light irradiance versus a residual value of just 16% measured at the same time in methanol solution. Further, degradation kinetic parameters of isotretinoin-loaded microemulsion formulation were demonstrated increase isotretinoin half-life about five-times in comparison with a methanol solution under a direct sun light.

Development and validation of an HPTLC method for determination of olanzapine in formulations.

A new, simple, and rapid HPTLC method was developed and validated for quantitative determination of olanzapine on silica gel 60F254 layers using methanol-ethyl acetate (8.0 + 2.0, v/v) as the mobile phase. Olanzapine was quantified by densitometric analysis at 285 nm. The method was found to give compact bands for the drug (Rf = 0.35 +/- 0.02). The linear regression analysis data for the calibration plots showed a good linear relationship with r2 = 0.9997 in the concentration range of 100-600 ng/band. The method was validated for precision, recovery, repeatability, and robustness as per the International Conference on Harmonization guidelines. The LOD was found to be 23.90 ng/band, and the LOQ was 91.04 ng/band. Statistical analysis of the data showed that the method is precise, accurate, reproducible, and selective for the analysis of olanzapine. The method was successfully used for the determination of equilibrium solubility and quantification of olanzapine as a bulk drug, in a commercially available preparation, and in in-house developed mucoadhesive microemulsion formulations and solution.

Simultaneous determination of alprazolam and fluoxetine hydrochloride in tablet formulations by high-performance column liquid chromatography and high-performance thin-layer chromatography.

This paper describes validated HPLC and HPTLC methods for simultaneous determination of alprazolam (ALP) and fluoxetine hydrochloride (FXT) in pure powder and formulation. The HPLC separation was achieved on a Nucleosil C8 column (150 mm length, 4.6 mm id, 5 microm particle size) using acetonitrile-phosphate buffer pH 5.5 (45 + 55, v/v) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using acetone-toluene-ammonia (6.0 + 3.5 + 0.5, v/v/v) as the mobile phase. Quantification in the HPLC method was achieved with UV detection at 230 nm over the concentration range 4-14 microg/mL for both drugs, with mean recovery of 99.95 +/- 0.38 and 99.85 +/- 0.56% for ALP and FXT, respectively. Quantification in the HPTLC method was achieved with UV detection at 230 nm over the concentration range of 400-1400 ng/spot for both drugs, with mean recovery of 99.32 +/- 0.45 and 99.78 +/- 0.81% for ALP and FXT, respectively. These methods are simple, precise, and sensitive, and they are applicable for the simultaneous determination of ALP and FXT in pure powder and formulations.

Effect of formulation components on the in vitro permeation of microemulsion drug delivery system of fluconazole.

The purpose of this study was to evaluate the effect of formulation components on the in vitro skin permeation of microemulsion drug delivery system containing fluconazole (FLZ). Lauryl alcohol (LA) was screened as the oil phase of microemulsions. The pseudo-ternary phase diagrams for microemulsion regions were constructed using LA as the oil, Labrasol (Lab) as the surfactant and ethanol (EtOH) as the cosurfactant. The formulation which showed a highest permeation rate of 47.15 +/- 1.12 microg cm(-2) h(-1) and appropriate physicochemical properties was optimized as containing 2% FLZ, 10% LA, 20% Lab/EtOH (1:1), and 68% double-distilled water (w/w). The efficiency of microemulsion formulation in the topical delivery of FLZ was dependent upon the contents of water and LA as well as Lab/EtOH mixing ratio. It was concluded that the percutaneous absorption of FLZ from microemulsions was enhanced with increasing the LA and water contents, and with decreasing the Lab/EtOH ratio in the formulation. Candida albicans was used as a model fungus to evaluate the antifungal activity of the best formula achieved, which showed the widest zone of inhibition as compared to FLZ reference. The studied microemulsion formulation showed a good stability for a period of 3 months. These results indicate that the studied microemulsion formulation might be a promising vehicle for topical delivery of FLZ.

Simultaneous estimation of acetylsalicylic acid and clopidogrel bisulfate in pure powder and tablet formulations by high-performance column liquid chromatography and high-performance thin-layer chromatography.

This paper describes validated high-performance column liquid chromatographic (HPLC) and high-performance thin-layer chromatographic (HPTLC) methods for simultaneous estimation of acetylsalicylic acid (ASA) and clopidogrel bisulfate (CLP) in pure powder and formulations. The HPLC separation was achieved on a Nucleosil C8 column (150 mm length x 4.6 mm id, 5 microm particle size) using acetonitrile-phosphate buffer, pH 3.0 (55 + 45, v/v) mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using ethyl acetate-methanol-toluene-glacial acetic acid (5.0 + 1.0 + 4.0 + 0.1, v/v/v/v) mobile phase. Quantitation was achieved with UV detection at 235 nm over the concentration range 4-24 microg/mL for both drugs, with mean recoveries of 99.98 +/- 0.28 and 100.16 +/- 0.66% for ASA and CLP, respectively, using the HPLC method. Quantitation was achieved with UV detection at 235 nm over the concentration range of 400-1400 ng/spot for both drugs, with mean recoveries of 99.93 +/- 0.55 and 100.21 +/- 0.83% for ASA and CLP, respectively, using the HPTLC method. These methods are simple, precise, and sensitive, and they are applicable for the simultaneous determination of ASA and CLP in pure powder and formulations.