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1.
Carbohydr Polym ; 251: 116871, 2021 Jan 01.
Article in English | MEDLINE | ID: mdl-33142550

ABSTRACT

Stimulated by researches in materials chemistry and medicine fields, drug delivery has entered a new stage of development. Drug delivery systems have been extensively studied according to the differences in the drug therapeutic environment such as pH, light, temperature, magnet, redox, enzymes, etc. Cyclodextrin is a smart tool that has been proven to be used in the preparation of drug delivery, and has become a new area of concern in recent years. In this review, we discuss recent research advances in smart stimuli-responsive cyclodextrin-based drug delivery. First, different stimuli-responsive drug delivery systems based on cyclodextrin are introduced and classified. Then, the characteristics of different types of stimuli-responsive drug delivery systems are described, and their applications are emphasized. Finally, current challenges and future development opportunities of smart stimuli-responsive drug delivery systems based on cyclodextrin are discussed.


Subject(s)
Cyclodextrins/chemistry , Drug Delivery Systems , Biocompatible Materials , Clinical Trials as Topic , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Enzymes/metabolism , Humans , Hydrogen-Ion Concentration , Light , Magnetics , Materials Testing , Oxidation-Reduction , Photochemical Processes , Temperature
2.
Mol Ther ; 27(10): 1706-1717, 2019 10 02.
Article in English | MEDLINE | ID: mdl-31526597

ABSTRACT

The field of cell and gene therapy (GT) is expanding rapidly and there is undoubtedly a wave of enthusiasm and anticipation for what these treatments could achieve next. Here we assessed the worldwide landscape of GT assets currently in early clinical development (clinical trial phase 1/2 or about to enter clinical trial). We included all gene therapies, i.e., strategies that modify an individual's protein make-up by introducing exogenous nucleic acid or nucleic acid modifiers, regardless of delivery. Unmodified cell therapies, oncology therapies (reviewed elsewhere), and vaccine programs (distinct therapeutic strategy) were not included. Using a December 31, 2018 cutoff date, we identified 336 gene therapies being developed for 138 different indications covering 165 genetic targets. In all, we found that the early clinical GT landscape comprises a very disparate group of drug candidates in terms of indications, organizations, and delivery methods. We also highlight interesting trends, revealing the evolution of the field toward in vivo therapies and adeno-associated virus vector-based delivery systems. It will be interesting to witness what proportion of this current list effectively translates into new medicines.


Subject(s)
Drug Delivery Systems/classification , Genetic Therapy/methods , Clinical Trials as Topic , Genetic Vectors/administration & dosage , Humans , Molecular Targeted Therapy
3.
Clin Microbiol Rev ; 32(2)2019 04.
Article in English | MEDLINE | ID: mdl-30651226

ABSTRACT

This review provides a comprehensive summary of issues associated with treating polyclonal bacterial biofilms in chronic diabetic wounds. We use this as a foundation and discuss the alternatives to conventional antibiotics and the emerging need for suitable drug delivery systems. In recent years, extraordinary advances have been made in the field of nanoparticle synthesis and packaging. However, these systems have not been incorporated into the clinic for treatments other than for cancer or severe genetic diseases. We present a unifying perspective on how the field is evolving and the need for an early amalgamation of engineering principles and a biological understanding of underlying phenomena in order to develop a therapy that is translatable to the clinic in a shorter time.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Diabetic Foot/microbiology , Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Coinfection , Diabetic Foot/drug therapy , Drug Delivery Systems/classification , Humans
4.
J Pharmacol Exp Ther ; 368(2): 255-261, 2019 02.
Article in English | MEDLINE | ID: mdl-30482795

ABSTRACT

Fewer new medicines have become available to patients during the last decades. Clinical efficacy failures in late-phase development have been identified as a common cause of this decline. Improved ways to ensure early selection of the right drug targets when it comes to efficacy is therefore a highly desirable goal. The aim of this work was to develop a strategy to facilitate selection of novel targets already in the discovery phase that later on in clinical development would demonstrate efficacy. A cross-functional team at AstraZeneca with extensive experience in drug discovery and development participated in several workshops to identify the critical elements that contribute to building human target validation [(HTV); the relevance of the target from a human perspective]. The elements were consolidated into a 10-point HTV classification system that was ranked from lowest to highest in terms of perceived impact on future clinical efficacy. Using 50 years of legacy research and development data, the ability of the 10-point HTV classification to predict future clinical efficacy was evaluated. Drug targets were classified as having low, medium, or high HTV at the time of candidate drug selection. Comparing this HTV classification with later clinical development efficacy data showed that HTV classification was highly predictive of future clinical efficacy success. This new strategy for HTV assessment provides a novel approach to early prediction of clinical efficacy and a better understanding of portfolio risk.


Subject(s)
Drug Delivery Systems/classification , Drug Delivery Systems/trends , Drug Development/classification , Drug Development/trends , Drug Delivery Systems/methods , Drug Development/methods , Forecasting , Humans , Reproducibility of Results , Treatment Outcome
5.
Crit Rev Ther Drug Carrier Syst ; 33(3): 265-308, 2016.
Article in English | MEDLINE | ID: mdl-27910752

ABSTRACT

A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting. They are designed mainly for pharmaceutical formulations suitable for various routes of administration like parenteral, ocular, transdermal, and oral. This review article describes the marked potential of submicron emulsions for oral drug delivery owing to their numerous advantages like reduced first pass metabolism, inhibition of P-glycoprotein efflux system, and enhanced absorption via intestinal lymphatic pathway. To overcome the limitations of liquid dosage forms, submicron emulsions can be formulated into solid dosage forms such as solid self-emulsifying systems. This article covers various types of submicron emulsions like microemulsion, nanoemulsion, and self-emulsifying drug delivery system (SEDDS), and their potential pharmaceutical applications in oral delivery with emphasis on their advantages, limitations, and advancements.


Subject(s)
Drug Delivery Systems/methods , Emulsions/administration & dosage , Nanoparticles/administration & dosage , Administration, Oral , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/classification , Emulsions/chemistry , Emulsions/classification , Humans , Models, Chemical
6.
Fed Regist ; 81(143): 48703-7, 2016 Jul 26.
Article in English | MEDLINE | ID: mdl-27459751

ABSTRACT

The Food and Drug Administration (FDA) is issuing a final order to reclassify iontophoresis devices intended for any other purposes, which are preamendments class III devices (regulated under product code EGJ), into class II (special controls) and to amend the device identification to clarify that devices intended to deliver specific drugs are not considered part of this regulatory classification.


Subject(s)
Device Approval/legislation & jurisprudence , Drug Delivery Systems/classification , Drug Delivery Systems/instrumentation , Iontophoresis/classification , Iontophoresis/instrumentation , Equipment Safety/classification , Humans , United States
7.
Curr Drug Metab ; 17(3): 279-91, 2016.
Article in English | MEDLINE | ID: mdl-26467064

ABSTRACT

BACKGROUND: Osmotic pump drug delivery systems are one of the most promising and widely developed systems. They are based on the principle of osmosis and are characterized by a zero-order release pattern independent of the physicochemical properties of the drug involved and some physiological factors. In the past 30 years, a series of difficulties, such as the very wide solubility range of different drugs, have been resolved accompanied by the development of various types of osmotic pumps. Furthermore, more advanced designs have been proposed according to practical requirements. METHODS: We started a systematic references collection on osmotic pump systems through different available databases. Then these information were analyzed and divided according to different subjects. Finally, we made clear our thought and begun to write it in a logical way. RESULTS: This review mainly concentrates on five kinds of functional osmotic pumps including technology combined, targeted, chronotherapy- based, ascending and compound osmotic pumps, involving ways to improve bioavailability and reduce side effects. Special attention is paid to the application of advanced imaging technologies to study osmotic pumps including the coating process, processing steps, polymer hydration and changes in the internal structure. CONCLUSIONS: Present-day osmotic pumps not only produce a constant release, but also have the ability to produce adjustable release according to practical requirements. Hence, technology combined, targeted, chronotherapy-based, ascending and compound osmotic pumps are a positive development. These latest advances offer various advantages compared with the classic osmotic pump, and enable them to meet the new needs for clinical use with fewer side effects and improved safety. In addition, following the improvements in the versatility and complexity of the novel osmotic pump system, conventional assessing parameters may fail to meet the increasing demand for information. Hence, novel imaging and monitoring technologies have been employed to monitor osmotic pumps from the coating process, processing steps, and polymer hydration to the changes in polymeric internal structure, which are associated with the different performance offered by the in vivo action of similar products.


Subject(s)
Drug Delivery Systems , Osmosis , Diagnostic Imaging , Drug Delivery Systems/classification , Humans , Pharmaceutical Preparations/administration & dosage , Pharmaceutical Preparations/chemistry
8.
Crit Rev Ther Drug Carrier Syst ; 32(2): 89-147, 2015.
Article in English | MEDLINE | ID: mdl-25955882

ABSTRACT

In this paper, we provide an overview an extensive range of colloidal drug delivery systems with special focus on vesicular and particulates systems that are being used in research or might be potentially useful as carriers systems for drug or active biomolecules or as cell carriers with application in the therapeutic field. We present some important examples of commercially available drug delivery systems with applications in research or in clinical fields. This class of systems is widely used due to excellent drug targeting, sustained and controlled release behavior, higher entrapment efficiency of drug molecules, prevention of drug hydrolysis or enzymatic degradation, and improvement of therapeutic efficacy. These characteristics help in the selection of suitable carrier systems for drug, cell, and gene delivery in different fields.


Subject(s)
Colloids , Drug Delivery Systems , Liposomes , Pharmaceutical Preparations/administration & dosage , Biological Therapy/methods , Colloids/classification , Colloids/pharmacology , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Drug Delivery Systems/trends , Forecasting , Humans , Liposomes/classification , Liposomes/pharmacology , Molecular Targeted Therapy/methods
9.
Crit Rev Ther Drug Carrier Syst ; 32(2): 149-80, 2015.
Article in English | MEDLINE | ID: mdl-25955883

ABSTRACT

Delivering therapeutics across the blood brain barrier (BBB) remains the rate-limiting step in brain medicine research. Three main categories of endogenous transportation at BBB that can be used for targeting brain are carrier-mediated transport, active efflux transport, and receptor-mediated transport. Various approaches using nanocarriers such as liposomes, niosomes, micelles, and nanoparticles with manifested surface modifications using either covalent or noncovalent methods to append suitable ligands are being intensively explored to achieve drug delivery to the brain. Harvested ligands include peptide, glutathione, transferrin, and transferrin antibody, lectins, lactic acid, cholera toxin B, etc. In this review, we present recent insights into the development of safe and efficient brain drug delivery as well as recent advances in BBB targeting tactics including antibody-directed enzyme prodrug therapy, a biotin-avidin conjugated system, and chimeric peptides. This review serves as an excellent source of knowledge for budding brain researchers.


Subject(s)
Biological Transport/physiology , Blood-Brain Barrier , Brain Diseases/drug therapy , Drug Delivery Systems , Ligands , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Humans , Prodrugs/pharmacology
10.
Adv Exp Med Biol ; 822: 195-8, 2015.
Article in English | MEDLINE | ID: mdl-25416990

ABSTRACT

This chapter deals with the classification of Drug Delivery nano Systems (DDnSs) with a Modulatory Controlled Release profile (MCR) denoted as Modulatory Controlled Release nano Systems (MCRnSs). Conventional (c) and advanced (a) DDnSs are denoted by the acronyms cDDnSs and aDDnSs, and can be composed of a single or more than one biomaterials, respectively. The classification was based on their characteristics such as surface functionality (f), the nature of biomaterials used, and the kind of interactions between biomaterials. The aDDnSs can be classified as Hybridic (Hy-) or Chimeric (Chi-) based on the nature-same or different, respectively-of biomaterials and inorganic materials used. The nature of the elements used for producing advanced biomaterials is of great importance and medicinal chemistry contributes effectively to the production of aDDnSs.


Subject(s)
Delayed-Action Preparations/administration & dosage , Drug Delivery Systems/methods , Nanostructures/administration & dosage , Nanotechnology/methods , Pharmaceutical Preparations/administration & dosage , Biocompatible Materials/chemistry , Delayed-Action Preparations/chemistry , Drug Delivery Systems/classification , Liposomes/chemistry , Nanostructures/chemistry , Pharmaceutical Preparations/chemistry , Reproducibility of Results
11.
Article in English | MEDLINE | ID: mdl-23658479

ABSTRACT

BACKGROUND: Ipratropium bromide/albuterol Respimat inhaler (CVT-R) was developed as an environmentally friendly alternative to ipratropium bromide/albuterol metered-dose inhaler (CVT-MDI), which uses a chlorofluorocarbon propellant. OBJECTIVE: The objective of this study was to evaluate patient satisfaction, device usage, and long-term safety of CVT-R compared to CVT-MDI, and to the simultaneous administration of ipratropium bromide hydrofluoroalkane (HFA; I) and albuterol HFA (A) metered-dose inhalers as dual monotherapies (I + A). DESIGN: This is a 48-week, open-label, randomized, active-controlled, parallel-group study (n = 470) comparing CVT-R to CVT-MDI and to I + A. PARTICIPANTS: Patients were at least 40 years of age, diagnosed with chronic obstructive pulmonary disease (COPD), and current or exsmokers. INTERVENTIONS: Patients were randomized to receive: (1) CVT-R, one inhalation four times daily (QID); or (2) CVT-MDI, two inhalations QID; or (3) I + A two inhalations of each inhaler QID. MAIN MEASURES: Patient Satisfaction and Preference Questionnaire (PASAPQ) performance score (primary endpoint) and adverse events. KEY RESULTS: PASAPQ performance score was significantly higher (CVT-R versus CVT-MDI, 9.6; and CVT-R versus I + A, 6.2; both P < 0.001) when using CVT-R compared to CVT-MDI or I + A at all visits starting from week 3, while CVT-MDI and I + A treatment groups were similar. Time to first COPD exacerbation was slightly longer in the CVT-R group compared to the other treatment groups, although it did not reach statistical significance (CVT-R versus CVT-MDI, P = 0.57; CVT-R versus I + A, P = 0.22). Rates of withdrawal and patient refusal to continue treatment were lower in CVT-R compared with CVT-MDI and I + A groups (CVT-R versus CVT-MDI, P = 0.09; CVT-R versus I + A, P = 0.005). The percentage of patients reporting adverse events and serious adverse events was similar across all three treatment groups. CONCLUSION: CVT-R is an effective, environmentally friendly inhaler that provides patients with a high level of user satisfaction and may positively impact clinical outcomes while having no adverse impacts on patients using the device.


Subject(s)
Airway Management/instrumentation , Albuterol , Ipratropium , Metered Dose Inhalers/standards , Nebulizers and Vaporizers/standards , Pulmonary Disease, Chronic Obstructive/drug therapy , Adult , Aged , Albuterol/administration & dosage , Albuterol/adverse effects , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Drug Combinations , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Drug Monitoring , Drug Therapy, Combination , Equipment Safety , Female , Humans , Ipratropium/administration & dosage , Ipratropium/adverse effects , Male , Middle Aged , Patient Preference , Treatment Outcome
12.
Respir Care ; 58(12): 2076-86, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23674810

ABSTRACT

BACKGROUND: Nebulized therapy is commonly used in spontaneously breathing tracheostomized patients, despite a lack of recommended devices and techniques. I compared albuterol dose delivered to a model of spontaneously breathing children with tracheostomy, using different nebulizers, tracheostomy tube sizes, inhalation techniques, and breathing patterns. METHODS: A tracheostomy model was connected in series to a breathing simulator, with a filter interposed. I simulated the breathing patterns of a 16-month-old child and 12-year-old child, and tested tracheostomy tubes with internal diameters of 3.5 mm and 5.5 mm. Albuterol nebulizer solution (2.5 mg/3 mL) was used. A breath-enhanced nebulizer (Pari LC Plus), a breath-actuated nebulizer (AeroEclipse), and a nebulizer that continuously delivers aerosol (Up-Draft II Opti-Neb) were operated for 5 min at 6 L/min with wall air. The Up-Draft II was tested with T-piece and mask interfaces, with an extension tube, and with and without assisted breathing (every breath and every other breath). The amount of albuterol delivered was analyzed via spectrophotometry. Particle size distribution was measured with a cascade impactor. RESULTS: The Pari LC Plus was more efficient than the Up-Draft II or AeroEclipse. Assisted breathing with the Up-Draft II with extension increased albuterol delivery with every other breath (second best device/configuration), being superior to every breath technique. Adding an extension tube increased delivered albuterol. T-piece was more efficient than mask. Breathing patterns with larger tidal volume increased albuterol delivery. Tracheostomy size had less impact on drug delivery. Mass median aerodynamic diameter decreased by 48-74% when passing through the tracheostomy tubes, and 0.8% of the nominal dose was deposited in the tracheostomy tube. CONCLUSIONS: Albuterol delivery in a model of spontaneously breathing children with tracheostomy is influenced by type of device and configuration, use of assisted breathing, breathing pattern, and tracheostomy tube size. Mass median aerodynamic diameter significantly decreases during passage through a tracheostomy tube.


Subject(s)
Bronchodilator Agents/administration & dosage , Drug Delivery Systems , Nebulizers and Vaporizers , Tracheostomy , Administration, Inhalation , Child , Computer Simulation , Drug Delivery Systems/classification , Drug Delivery Systems/instrumentation , Drug Delivery Systems/methods , Equipment Design , Humans , Models, Biological , Respiration/drug effects , Tracheostomy/instrumentation , Tracheostomy/methods
13.
Eur J Pharm Biopharm ; 84(3): 445-8, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23333302

ABSTRACT

There is an increasing discussion about potential toxicity of nanoparticles (nanotoxicity). A classification system is proposed classifying the nanoparticles in four classes (I to IV) from low/no risk to high risk. It is based on the nanoparticle size (>/<100 nm) and size-related differences in interaction with human cells, and on biodegradability/non-biodegradability in the body. This classification is superimposed by biocompatibility (B) and non-biocompatibility (NB) of the nanoparticle surface, resulting in a total of eight classes from I-B (best tolerated) to IV-NB (highest potential risk). The classification should help as a guideline in pharmaceutical formulation development, but also as a guide for risk assessment in other product areas and environmental exposure.


Subject(s)
Drug Delivery Systems/classification , Nanomedicine/methods , Nanoparticles/chemistry , Nanoparticles/classification , Nanotechnology/methods , Chemistry, Pharmaceutical/methods , Drug Design , Humans , Nanoparticles/toxicity , Particle Size , Risk Assessment , Surface Properties
14.
EuroIntervention ; 8(4): 444-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22917727

ABSTRACT

AIMS: Recently, drug-eluting balloons have received a guideline class IIa recommendation in the treatment of in-stent restenosis after bare metal stent implantation. It is not known if different balloons perform equally. Using a large real world registry, restenosis frequency was reported for two drug-eluting balloons. METHODS AND RESULTS: From April 2009 until September 2011, 1,129 patients were treated with paclitaxel-eluting balloons in Sweden. Mean follow-up was 328 ± 210 days. Nine hundred and nineteen patients were treated with a balloon using a contrast agent as a drug-carrier and 217 with a balloon without a contrast agent as a drug-carrier. The indications were predominantly de novo (45.4%) or in-stent restenotic (51.8%) lesions. The overall incidence of restenosis at six months was 3.4% with the paclitaxel balloon using a contrast agent as carrier, compared with 12.5% with the paclitaxel-eluting balloon without a carrier (risk ratio: 0.42; 95% confidence interval [CI] [0.26-0.68]). After adjusting for indications, lesion types and procedural factors, the risk ratio was 0.39; 95% CI (0.24-0.65). CONCLUSIONS: This observational study from a large real world population shows a major difference between two paclitaxel-eluting balloons. The findings suggest that there are no class effects for drug-eluting balloons and factors other than the drug may be important for the clinical effect.


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Restenosis/prevention & control , Drug Delivery Systems/instrumentation , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Aged , Angioplasty, Balloon, Coronary/classification , Angioplasty, Balloon, Coronary/methods , Coronary Restenosis/drug therapy , Coronary Restenosis/epidemiology , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Registries , Regression Analysis , Retrospective Studies , Risk Factors , Sweden , Treatment Outcome
15.
Vet J ; 193(1): 12-23, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22365842

ABSTRACT

Nanomedicine is a rapidly expanding field with a promising future that is already permeating veterinary science. This review summarises the current applications for nanoparticles in human medicine and explores their potential applicability for veterinary use. The principles underlying the use of nanoparticles in drug delivery, imaging and as vaccine adjuvants are explored along with the unique issues surrounding nanoparticle toxicity and regulatory approval. A brief overview of the properties of different nanoparticle systems including, liposomes, micelles, emulsions and inorganic nanoparticles, is provided, along with a description of their current and potential future applications in veterinary medicine.


Subject(s)
Drug Delivery Systems/veterinary , Nanomedicine/methods , Veterinary Medicine/methods , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Drug Delivery Systems/standards , Nanomedicine/standards , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Veterinary Medicine/standards
16.
J Pharm Pharmacol ; 62(11): 1622-36, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21039546

ABSTRACT

OBJECTIVES: The aim of this review is to highlight relevant considerations when implementing a rational strategy for the development of lipid and surfactant based drug delivery system and to discuss shortcomings and challenges to the current classification of these delivery systems. We also aim to offer suggestions for an improved classification system that will accommodate lipid based formulations that are not currently accommodated in the lipid formulation classification system. KEY FINDINGS: When categorising lipid and surfactant based drug delivery systems, the current Lipid Formulations Classifications System is a useful tool. However, it does not apply to all marketed lipid and surfactant systems or those reported in research papers. A more profound understanding of the functionalities of lipids and surfactants and their role in emulsion formation will enable a rational development strategy and will create the basis for a revised classification system encompassing all employed lipid and surfactant drug delivery systems. SUMMARY: The ever-increasing number of poorly soluble compounds in drug discovery and development calls for the serious need for effective and affordable drug delivery strategies that will enhance bioavailability and decrease variability. Lipid and surfactant based drug delivery systems offer these advantages; however, the development of these systems requires proper understanding of the physicochemical nature of the compound as well as the lipid excipients and gastrointestinal digestion. One major challenge of lipid excipients and delivery systems is the varying range of compounds they contain. This has contributed to the challenge of proper characterisation and evaluation of these delivery systems, their stability, classification and regulatory issues, which consequently have affected the number of these formulations that eventually reach the market. Suggestions as to proper classification of these delivery systems based on their main lipid component and recommended use are put forward. The prospect of these delivery systems looks promising.


Subject(s)
Drug Delivery Systems , Lipids/chemistry , Pharmaceutical Preparations/administration & dosage , Surface-Active Agents/chemistry , Administration, Oral , Biological Availability , Drug Delivery Systems/classification , Emulsions/chemistry , Emulsions/classification , Lipids/classification , Pharmaceutical Preparations/chemistry , Solubility , Surface-Active Agents/classification , Technology, Pharmaceutical/methods
17.
J Drug Target ; 18(6): 413-9, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20132094

ABSTRACT

The term pulsatile drug delivery has often been used as a synonym to chronotherapeutic drug delivery. This needs to be given a thought as both the drug delivery systems are entirely addressing different needs of the patients as well as the intentions of the formulators being different. Chronotherapeutic systems are based completely on circadian needs and response of the body and the need of the drug to be in its maximum concentrations at a particular time of the day, the fact being supported by endless list of ailments which elicit the related symptoms at a particular time of the day. Considering the formulation approach, one does not find major differences among site-specific chronotherapeutic systems and the basic and more conventional intestinal or colon targeted systems due to the mechanism and the site of landing of drug of both being almost similar even though the intention of the formulator being different. An ideal pulsatile system is the one delivering drug in different pulses with multiple troughs in release profile. The article explores the major differences in between the two systems and highlights the need of using appropriate terminology for these individual and distinct systems catering different needs.


Subject(s)
Drug Chronotherapy , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Pharmaceutical Preparations/administration & dosage , Pulse Therapy, Drug , Chemistry, Pharmaceutical , Humans , Pharmaceutical Preparations/blood , Pharmaceutical Preparations/chemistry , Terminology as Topic
18.
Mov Disord ; 24(9): 1319-24, 2009 Jul 15.
Article in English | MEDLINE | ID: mdl-19412946

ABSTRACT

Controlled-release carbidopa and levodopa (CL-CR) and the combination of carbidopa, levodopa, and entacapone (CLE) are used for extending levodopa (L-dopa) effects. In a randomized, open-label crossover study of 17 PD subjects with wearing-off responses, we compared 8-hour L-dopa pharmacokinetics (PK) and clinical effects after two doses of CL-CR (50 and 200 mg, respectively) and CLE (37.7, 150, 200 mg, respectively). PK analysis revealed the anticipated near-equivalent mean L-dopa area-under-the-concentration-curve values (639,490 ng min/mL for two doses of CLE, and 662,577 for CL-CR, P = 0.86). The mean hourly fluctuation index for L-dopa concentration was 235% for CLE and 196% for CL-CR (P = 0.004). The mean maximal concentration for the first CLE dose was 1,926 +/- 760 ng/mL and for CL-CR, 1,840 +/- 889 (P = 0.33). During the PK studies, the mean time that L-dopa concentration was > or =1,000 ng/mL for CLE was 291 +/- 88 minutes and for CL-CR, 306 +/- 86 (P = 0.33). The mean percent-time in "off" state was 18% for CLE and 28% for CL-CR (P = 0.017), "on state without dyskinesia" was 64% for CLE and 65% for CL-CR (P = 0.803), and "on state with nontroublesome dyskinesia" was 18% for CLE and 7% for CL-CR (P = 0.03). Despite less "off" time with CLE, both formulations demonstrated similar mean PK values and marked intersubject PK variability.


Subject(s)
Antiparkinson Agents/pharmacokinetics , Carbidopa/pharmacokinetics , Catechols/pharmacokinetics , Nitriles/pharmacokinetics , Parkinson Disease/blood , Aged , Analysis of Variance , Antiparkinson Agents/blood , Antiparkinson Agents/therapeutic use , Carbidopa/therapeutic use , Catechols/therapeutic use , Cross-Over Studies , Disability Evaluation , Dose-Response Relationship, Drug , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Drug Therapy, Combination , Female , Humans , Levodopa/blood , Levodopa/pharmacokinetics , Levodopa/therapeutic use , Male , Middle Aged , Nitriles/therapeutic use , Parkinson Disease/drug therapy , Retrospective Studies , Severity of Illness Index , Time Factors
19.
Br J Pharmacol ; 153(3): 432-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17700724

ABSTRACT

Drugs are named for their primary receptor target and overt action (agonism, antagonism) but the observation of multiple or collateral efficacies emanating from drugs activating a single receptor target is posing a challenge for drug classification and nomenclature. With increasing abilities to detect alteration in cellular function has come the identification of efficacies that are not necessarily manifest in obvious changes in cell response. Specifically, some agonists selectively activate cellular pathways, demonstrate phenotypic behaviour associated with cell type and some antagonists actively induce receptor internalization without activation. In addition, the effects of allosteric modulators can be linked to the nature of the co-binding ligand posing a similar complication in classification and naming. Thus, accurate labels for this new generation of selective drugs may require identification of receptor partners (G-protein type, beta-arrestin) or pathway or, in the case of allosteric modulators, identification of co-binding ligands. The association of distinct phenotypic behaviours with molecules opens the opportunity to better associate clinical effects with distinct pharmacological properties.


Subject(s)
Drug Delivery Systems/classification , Pharmaceutical Preparations/classification , Terminology as Topic , Allosteric Regulation , Drug Agonism , Drug Antagonism , Humans , Ligands
20.
Eur J Pharm Biopharm ; 66(1): 34-41, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17070678

ABSTRACT

This study was aimed at developing a polymeric drug delivery system for a new and potent antitumor drug, 9-nitrocamptothecin (9-NC), intended for both intravenous administration and improving the therapeutic index of the drug. To achieve these goals, 9-NC loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared by nanoprecipitation method and characterized. The full factorial experimental design was used to study the influence of four different independent variables on response of nanoparticle drug loading. Analysis of variance (ANOVA) was used to evaluate optimized conditions for the preparation of nanoparticles. The physical characteristics of PLGA nanospheres were evaluated using particle size analyzer, scanning electron microscopy, differential scanning calorimetry and X-ray diffractometry. The results of optimized formulations showed a narrow size distribution with a polydispersity index of 0.01%, an average diameter of 207+/-26 nm, and a drug loading of more than 30%. The in vitro drug release profile showed a sustained 9-NC release up to 160 h indicating the suitability of PLGA nanoparticles in controlled 9-NC release. Thus prepared nanoparticles described here may be of clinical importance in both stabilizing and delivering camptothecins for cancer treatment.


Subject(s)
Antineoplastic Agents/pharmacology , Camptothecin/analogs & derivatives , Drug Compounding/methods , Nanoparticles/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Biocompatible Materials/chemistry , Calorimetry, Differential Scanning , Camptothecin/administration & dosage , Camptothecin/chemistry , Camptothecin/pharmacokinetics , Drug Delivery Systems/classification , Drug Delivery Systems/methods , Lactic Acid/chemistry , Microscopy, Electron, Scanning , Models, Theoretical , Molecular Structure , Nanoparticles/administration & dosage , Nanoparticles/ultrastructure , Particle Size , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Polymers/chemistry , Research Design , Technology, Pharmaceutical/methods , X-Ray Diffraction
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