Systematic Development and Optimization of an in-situ Gelling System for Moxifloxacin Ocular Nanosuspension using High-pressure Homogenization with an Improved Encapsulation Efficiency.

Abstract:

BACKGROUND:The objective of this study was to apply Quality by Design (QbD) principles on process parameter optimization for the development of hybrid delivery system (combination of (SLNs) and In-situ gelling system) for hydrophilic drug Moxifloxacin Hydrochloride (MOX) to achieve its controlled delivery, which otherwise may not be possible through single type of technology. METHODS:Risk assessment studies were carried out to identify probable risks influencing CQAs on the product. In design of experiments (DoE), the process parameters (independent variables) i.e., chiller temperature X1, High Pressure Homogenization (HPH) pressure X2, and HPH cycles X3 were optimized using a three-factor two level face-centered central composite design to streamline the influence on three responses, namely encapsulation efficiency Y1, particle size Y2 and outlet temperature Y3. Independent and dependent variables were analyzed to establish a full-model second-order polynomial equation. F value is used to confirm the omission of insignificant parameters/interactions to derive a reduced-model polynomial equation to predict the Y1, Y2 and Y3 for optimized moxifloxacin in situ gelled nanosuspension. RESULTS:Desirability plots showed the effects of X1, X2, and X3 on Y1, Y2 and Y3, respectively. The design space is generated to obtain optimized process parameters viz. chiller temperature (-5°C), HPH pressure 800 - 900 bar and 8 cycles that resulted in nanosuspension with ≈ 500 nm size, encapsulation efficiency >65% and final formulation temperature <23°C that were necessary to maintain the formulation in a liquid state. CONCLUSION:Quality by Design (QbD) approach is recently been encouraged by regulatory bodies to improve the quality of the finished product. This approach proved to be a useful tool in the development of robust nanosuspension of highly hydrophilic drugs with improved efficiency. Results indicate that such hybrid gel systems can be used to control the release of SLNs from application site and prolong their action in a sustained manner.

journal_name

Curr Pharm Des

authors

Khurana LK,Singh R,Singh H,Sharma M

doi

10.2174/1381612824666180403115106

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

1434-1445

issue

13

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-89476

journal_volume

24

pub_type

杂志文章
  • G protein-coupled receptors and their signaling pathways: classical therapeutical targets susceptible to novel therapeutic concepts.

    abstract::In recent years, new strategies in cancer therapy have been developed targeting key signaling molecules in the receptor tyrosine kinase signal transduction pathway. In contrast, most therapeutical concepts to manipulate G protein-coupled receptors (GPCR)-mediated disorders are still limited to the use of receptor-spec...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612043384367

    authors: Liebmann C

    更新日期:2004-01-01 00:00:00

  • Naoxintong protects against atherosclerosis through lipid-lowering and inhibiting maturation of dendritic cells in LDL receptor knockout mice fed a high-fat diet.

    abstract::Naoxintong (NXT), a Chinese Materia Medica standardized product, extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinennsis, Astragali Radix, is clinically effective in treating atherosclerosisrelated diseases. Here, we tested the hypothesis that the anti-...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612811319330008

    authors: Zhao J,Zhu H,Wang S,Ma X,Liu X,Wang C,Zhao H,Fan S,Jin X,Zhao B,Zhao T,Jia L,Wang K,Zou Y,Hu K,Sun A,Ge J

    更新日期:2013-01-01 00:00:00

  • Ectopic ATP synthase in endothelial cells: a novel cardiovascular therapeutic target.

    abstract::Adenosine triphosphate (ATP) synthase produces ATP in cells and is found on the inner membrane of mitochondria or the cell plasma membrane (ectopic ATP synthase). Here, we summarize the functions of ectopic ATP synthase in vascular endothelial cells (ECs). Ectopic ATP synthase is involved in adenosine metabolism on th...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210794519219

    authors: Fu Y,Zhu Y

    更新日期:2010-01-01 00:00:00

  • Interactive endogenous small molecule (gaseous) signaling: implications for teratogenesis.

    abstract::Dioxygen (O2) is an exogenously supplied gas with a number of properties that make it valuable as a biological source of energy and as a result much of life has become dependent on this molecule. Nitric oxide (NO), carbon dioxide (CO) and hydrogen sulfide (H2S) are small molecules that are sometimes in a gaseous state...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161207782110525

    authors: Fukuto JM,Collins MD

    更新日期:2007-01-01 00:00:00

  • Physiology and therapeutic potential of the thymic peptide thymulin.

    abstract::Thymulin is a thymic hormone exclusively produced by the epithelial cells of the thymus. After its discovery and initial characterization in the '70s, it was demonstrated that the production and secretion of thymulin are strongly influenced by the neuro-endocrine system. Conversely, a growing body of evidence, to be r...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612820666140130211157

    authors: Reggiani PC,Schwerdt JI,Console GM,Roggero EA,Dardenne M,Goya RG

    更新日期:2014-01-01 00:00:00

  • Pulmonary surfactant proteins A and D: innate immune functions and biomarkers for lung diseases.

    abstract::Pulmonary surfactant, a complex of lipids and proteins, functions to keep alveoli from collapsing at expiration. Surfactant proteins A (SP-A) and D (SP-D) belong to the collectin family and play pivotal roles in the innate immunity of the lung. Pulmonary collectins directly bind with broad specificities to a variety o...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206775474387

    authors: Takahashi H,Sano H,Chiba H,Kuroki Y

    更新日期:2006-01-01 00:00:00

  • Adhesion Molecules as Potential Novel Biomarkers for Opioid Dependence.

    abstract:BACKGROUND:Cell-cell adhesion is essential in maintaining the structure and function of an organ. Several adhesion molecules have recently been identified as associated with heroin dependence in both genetic and peripheral plasma studies. METHODS AND RESULTS:We reviewed literature concerning studies on adhesion molecu...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612826666200116144147

    authors: Liu YL,Kuo HW,Fang CP,Tsung JH,Chen ACH

    更新日期:2020-01-01 00:00:00

  • Effect of SDF-1 α on endogenous mobilized and transplanted stem cells in regeneration after myocardial infarction.

    abstract::Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1α) in mobilizing stem cells in combination with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine ischemia/reperfusion model. Initially bone marrow was eradi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/13816128113199990443

    authors: Schuh A,Konschalla S,Kroh A,Schober A,Marx N,Sonmez TT,Zenke M,Sasse A,Liehn EA

    更新日期:2014-01-01 00:00:00

  • Circular micro-proteins and mechanisms of cyclization.

    abstract::Transpeptidation reactions result in the formation of new peptide bonds and this can occur between two separate peptides or within the one peptide. These reactions are catalyzed by enzymes and when the N- and C-terminus of the one peptide are joined it results in the formation of cyclic proteins. Cyclization via head-...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161211798999410

    authors: Conlan BF,Anderson MA

    更新日期:2011-12-01 00:00:00

  • Platelet-neutrophil interactions as a target for prevention and treatment of transfusion-related acute lung injury.

    abstract::Transfusion-related acute lung injury (TRALI) is a major cause of morbidity and mortality in transfused hosts and like other causes of acute lung injury, there is no effective pharmacologic treatment. The pathophysiology of TRALI is still being defined, but neutrophils have a major role in the pathogenesis of both hum...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811209023260

    authors: Caudrillier A,Looney MR

    更新日期:2012-01-01 00:00:00

  • Understanding the Binding Mechanism of Amyloid-β Inhibitors from Molecular Simulations.

    abstract::In recent years, Aβ aggregation prevention, one of the most concerned strategies in drug development has been carefully assessed to treat Alzheimer's disease. Aβ peptides can transform structurally from random coil monomer into β-stranded protofibril via multiple oligomeric states. Among the various Aβ species, the id...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612824666180813093420

    authors: Tran L

    更新日期:2018-01-01 00:00:00

  • Inflammatory mediators in epilepsy.

    abstract::All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the prop...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319380009

    authors: Lorigados Pedre L,Morales Chacón LM,Orozco Suárez S,Pavón Fuentes N,Estupiñán Díaz B,Serrano Sánchez T,García Maeso I,Rocha Arrieta L

    更新日期:2013-01-01 00:00:00

  • Depression in older persons with mobility limitations.

    abstract::The impact of depression on physical disability is undisputed. There is convincing evidence that depression increases the subsequent risk for physical disability and, in turn, physical disability results in increased depressive symptoms. Moreover, depression affects also the earlier stages of the disablement process (...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113196660060

    authors: Milaneschi Y,Penninx BW

    更新日期:2014-01-01 00:00:00

  • Opioid receptors and their ligands in the musculoskeletal system and relevance for pain control.

    abstract::Interest in opioid drugs like morphine, as the oldest and most potent pain-killing agents known, has been maintained through the years. One of the most frequent chronic pain sensations people experience is associated with pathological conditions of the musculoskeletal system. Chronic musculoskeletal pain is a major he...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113199990363

    authors: Spetea M

    更新日期:2013-01-01 00:00:00

  • Can mycobacterial genomics generate novel targets as speed-breakers against the race for drug resistance.

    abstract::The rise of multi-drug resistant and extensively drug resistant M. tuberculosis around the world poses a great threat to human health, and necessitates development of new, effective and inexpensive anti-tubercular agents. The availability of knowledge on molecular biology of M. tuberculosis infection coupled with whol...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612819666131118165427

    authors: Chauhan RS,Chanumolu SK,Rout C,Shrivastava R

    更新日期:2014-01-01 00:00:00

  • Activation of the Glutathione Peroxidase by Metformin in the Bile-duct Ligation induced Liver Injury: In vivo Combined with Molecular Docking Studies.

    abstract:BACKGROUND:Inhibition of hepatic fibrosis is an attainable objective in managing the chronic liver disease. The present study aimed to investigate possible defensive effects of metformin on the activities of antioxidant enzymes, hydroxyproline content, and biochemical factors in bile duct ligation (BDL)-induced cholest...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612824666181003114108

    authors: Mansourian M,Sadeghi H,Doustimotlagh AH

    更新日期:2018-01-01 00:00:00

  • Proprotein Convertase Subtilisin/kexin type 9 Inhibition in Cardiovascular Prevention.

    abstract::Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDLC and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite hi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612824666180111105201

    authors: Ali A,Costanzo P,Hoye A

    更新日期:2018-01-01 00:00:00

  • Cholinesterase Inhibitors for Alzheimer's Disease: Multitargeting Strategy Based on Anti-Alzheimer's Drugs Repositioning.

    abstract::In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improveme...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612825666191008103141

    authors: Kabir MT,Uddin MS,Begum MM,Thangapandiyan S,Rahman MS,Aleya L,Mathew B,Ahmed M,Barreto GE,Ashraf GM

    更新日期:2019-01-01 00:00:00

  • Gender differences in the clinical presentation of heart disease.

    abstract::The clinical presentation of heart disease is different between men and women and this distinction is pivotal for a correct diagnosis and an adequate treatment. However, the definition of symptoms classically associated with heart disease is mainly based on the characteristics of those reported in men. Chest pain or c...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/138161211795656927

    authors: Collins P,Vitale C,Spoletini I,Barbaro G

    更新日期:2011-01-01 00:00:00

  • The role of protonation states in ligand-receptor recognition and binding.

    abstract::In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319230004

    authors: Petukh M,Stefl S,Alexov E

    更新日期:2013-01-01 00:00:00

  • Veterinary vaccines from transgenic plants: highlights of two decades of research and a promising example.

    abstract::In the last two decades the development of efficient plant-based expression strategies and new concepts for the purification of recombinant proteins prompted the application of plant-derived vaccines for veterinary purposes. The expression of recombinant proteins in plants possesses advantages over conventional eukary...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612811319310014

    authors: Phan HT,Floss DM,Conrad U

    更新日期:2013-01-01 00:00:00

  • Actions of selected cardiovascular hormones on arterial stiffness and wave reflections.

    abstract::The large conduit arteries of the thorax and abdomen are elastic while those in the arms and legs are muscular. Alterations in wall properties of elastic arteries occur over time and are usually permanent in nature; acute changes can, however, occur is response to a change in transmural pressure. Chronic alterations i...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161209787354258

    authors: Nichols WW,Epstein BJ

    更新日期:2009-01-01 00:00:00

  • Role of copper in prion diseases: deleterious or beneficial?

    abstract::Prion diseases are fatal neurodegenerative disorders associated with conformational conversion of the cellular prion protein (PrP(C)) into an isoform designated PrP(Sc). The pathogenic mechanism that links this conformational distortion with the development of prion diseases is unknown. PrP(C) is a GPI-anchored cell s...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161206777698873

    authors: Varela-Nallar L,González A,Inestrosa NC

    更新日期:2006-01-01 00:00:00

  • Roles of cardiovascular risk factors in endothelial nitric oxide synthase regulation: an update.

    abstract::Cardiovascular disease remains the number one killer in the United States and many other countries. Each year, there are enormous research efforts on its pathogenesis, prevention and treatment led by scientists worldwide. One of the most significant research areas is the impact and mechanisms of existing or new cardio...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113196660744

    authors: Jamaluddin MS,Liang Z,Lu JM,Yao Q,Chen C

    更新日期:2014-01-01 00:00:00

  • Designing decoys for chemokine-chemokine receptor interaction.

    abstract::Aberrant expression of chemokines and their receptors play causative roles in the pathophysiology of numerous autoimmune and inflammatory disease processes. Moreover, an integral step in HIV infection involves binding to chemokine receptors, and hence chemokines are intimately linked to HIV-related diseases. Therefore...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612023393233

    authors: Rajarathnam K

    更新日期:2002-01-01 00:00:00

  • Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19).

    abstract:BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes ...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章

    doi:10.2174/1381612826666200707121636

    authors: Lovato ECW,Barboza LN,Wietzikoski S,de Souza ANV,Auth PA,Junior AG,Dos Reis Lívero FA

    更新日期:2020-07-07 00:00:00

  • Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the elderly. The increase of life-expectancy is transforming AD into a major health-care problem. AD is characterized by a progressive impairment of memory and other cognitive skills leading to dementia. The major pathogenic factor ass...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161210793176572

    authors: Agostinho P,Cunha RA,Oliveira C

    更新日期:2010-01-01 00:00:00

  • Transcranial Direct Current Stimulation for the Treatment of Refractory Symptoms of Schizophrenia. Current Evidence and Future Directions.

    abstract::Schizophrenia is a severe and frequent neuropsychiatric disorder. Despite antipsychotic medications, up to 30% of patients with schizophrenia still report disabling treatment-resistant symptoms. Transcranial direct current stimulation (tDCS) has been proposed as a novel method to alleviate such symptoms. Here, we revi...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/1381612821666150619093648

    authors: Mondino M,Brunelin J,Palm U,Brunoni AR,Poulet E,Fecteau S

    更新日期:2015-01-01 00:00:00

  • Mitochondrial drug targets in cell death and cancer.

    abstract::Mitochondria are involved in different physiological and pathological processes that are crucial for tumor cell physiology, growth and survival. Since cancer cells have frequently disrupted different cell death pathways that promote their survival, mitochondria may be key organelles to promote cell death in cancer cel...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/138161211796904803

    authors: Ferrín G,Linares CI,Muntané J

    更新日期:2011-01-01 00:00:00

  • Small cationic antimicrobial peptidomimetics: emerging candidate for the development of potential anti-infective agents.

    abstract::Rapid increase in the emergence and spread of microbes resistant to conventionally used antibiotics has become a major threat to global health care. Antimicrobial peptides (AMPs) are considered as a potential source of novel antibiotics because of their numerous advantages such as broad-spectrum activity, lower tenden...

    journal_title:Current pharmaceutical design

    pub_type: 杂志文章,评审

    doi:10.2174/13816128113199990003

    authors: Lohan S,Bisht GS

    更新日期:2013-01-01 00:00:00