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Pharmaceutics, Volume 6, Issue 1 (March 2014), Pages 1-194

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Editorial

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Open AccessEditorial Acknowledgement to Reviewers of Pharmaceutics in 2013
Pharmaceutics 2014, 6(1), 78-79; doi:10.3390/pharmaceutics6010078
Received: 28 February 2014 / Accepted: 28 February 2014 / Published: 28 February 2014
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Abstract The editors of Pharmaceutics would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2013. [...] Full article

Research

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Open AccessArticle Electrostatic Charge Effects on Pharmaceutical Aerosol Deposition in Human Nasal–Laryngeal Airways
Pharmaceutics 2014, 6(1), 26-35; doi:10.3390/pharmaceutics6010026
Received: 13 September 2013 / Revised: 23 January 2014 / Accepted: 26 January 2014 / Published: 29 January 2014
Cited by 11 | PDF Full-text (1346 KB) | HTML Full-text | XML Full-text
Abstract
Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the
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Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN) k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessArticle Performance of Dry Powder Inhalers with Single Dosed Capsules in Preschool Children and Adults Using Improved Upper Airway Models
Pharmaceutics 2014, 6(1), 36-51; doi:10.3390/pharmaceutics6010036
Received: 20 December 2013 / Revised: 20 January 2014 / Accepted: 23 January 2014 / Published: 6 February 2014
Cited by 4 | PDF Full-text (366 KB) | HTML Full-text | XML Full-text
Abstract
The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction
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The pulmonary administration of pharmaceutical aerosols to patients is affected by age-dependent variations in the anatomy of the upper airways and the inhalation pattern. Considering this aspect, different upper airway models, representing the geometries of adults and preschool children, and a conventional induction port according to the European Pharmacopeia were used for in vitro testing of dry powder inhalers with single dosed capsules (Cyclohaler®, Handihaler® and Spinhaler®). Deposition measurements were performed using steady flow rates of 30 and 60 L/min for the Handihaler®/Spinhaler® and 30, 60 and 75 L/min for the Cyclohaler®. The inhalation volume was set at 1 L. For the Cyclohaler®, the in vitro testing was supplemented by a pediatric inhalation profile. Slight differences of pulmonary deposition between the idealized adult (11%–15%) and pediatric (9%–11%) upper airway model were observed for the Cyclohaler®. The applied pediatric inhalation profile resulted in a reduction of pulmonary deposition by 5% compared to steady conditions and indicated the influence of the inhalation pattern on the amount of pulmonary deposited particles. The comparison of two pediatric upper airway models showed no differences. The performance of the Handihaler® was similar to the Cyclohaler®. The Spinhaler® showed an insufficient performance and limited reproducibility in our investigations. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessArticle Development of a Physiologically-Based Pharmacokinetic Model of the Rat Central Nervous System
Pharmaceutics 2014, 6(1), 97-136; doi:10.3390/pharmaceutics6010097
Received: 7 November 2013 / Revised: 26 February 2014 / Accepted: 6 March 2014 / Published: 18 March 2014
Cited by 1 | PDF Full-text (1591 KB) | HTML Full-text | XML Full-text
Abstract
Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of
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Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways. Full article
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Open AccessArticle Encapsulation of Alcohol Dehydrogenase in Mannitol by Spray Drying
Pharmaceutics 2014, 6(1), 185-194; doi:10.3390/pharmaceutics6010185
Received: 17 January 2014 / Revised: 27 February 2014 / Accepted: 13 March 2014 / Published: 24 March 2014
Cited by 1 | PDF Full-text (1856 KB) | HTML Full-text | XML Full-text
Abstract
The retention of the enzyme activity of alcohol dehydrogenase (ADH) has been studied in various drying processes such as spray drying. The aim of this study is to encapsulate ADH in mannitol, either with or without additive in order to limit the thermal
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The retention of the enzyme activity of alcohol dehydrogenase (ADH) has been studied in various drying processes such as spray drying. The aim of this study is to encapsulate ADH in mannitol, either with or without additive in order to limit the thermal denaturation of the enzyme during the drying process. The retention of ADH activity was investigated at different drying temperatures. When mannitol was used, the encapsulated ADH was found inactive in all the dried powders. This is presumably due to the quick crystallization of mannitol during spray drying that resulted in the impairment of enzyme protection ability in comparison to its amorphous form. Maltodextin (dextrose equivalent = 11) was used to reduce the crystallization of mannitol. The addition of maltodextrin increased ADH activity and drastically changed the powder X-ray diffractogram of the spray-dried powders. Full article
(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics 2014)
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Review

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Open AccessReview Phototriggerable Liposomes: Current Research and Future Perspectives
Pharmaceutics 2014, 6(1), 1-25; doi:10.3390/pharmaceutics6010001
Received: 11 November 2013 / Revised: 28 November 2013 / Accepted: 5 December 2013 / Published: 19 December 2013
Cited by 17 | PDF Full-text (1181 KB) | HTML Full-text | XML Full-text
Abstract
The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and
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The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules including drugs, pharmaceutical agents and nucleic acids. Among these, drug delivery technology has made discernible progress in recent years and the areas that warrant further focus and consideration towards technological developments have also been recognized. Development of viable methods for on-demand spatial and temporal release of entrapped drugs from the nanocarriers is an arena that is likely to enhance the clinical suitability of drug-loaded nanocarriers. One such approach, which utilizes light as the external stimulus to disrupt and/or destabilize drug-loaded nanoparticles, will be the discussion platform of this article. Although several phototriggerable nanocarriers are currently under development, I will limit this review to the phototriggerable liposomes that have demonstrated promise in the cell culture systems at least (but not the last). The topics covered in this review include (i) a brief summary of various phototriggerable nanocarriers; (ii) an overview of the application of liposomes to deliver payload of photosensitizers and associated technologies; (iii) the design considerations of photoactivable lipid molecules and the chemical considerations and mechanisms of phototriggering of liposomal lipids; (iv) limitations and future directions for in vivo, clinically viable triggered drug delivery approaches and potential novel photoactivation strategies will be discussed. Full article
(This article belongs to the Special Issue Liposome Technologies)
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Open AccessReview Overcoming the Cutaneous Barrier with Microemulsions
Pharmaceutics 2014, 6(1), 52-77; doi:10.3390/pharmaceutics6010052
Received: 16 December 2013 / Revised: 24 January 2014 / Accepted: 11 February 2014 / Published: 28 February 2014
Cited by 18 | PDF Full-text (327 KB) | HTML Full-text | XML Full-text
Abstract
Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple
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Microemulsions are fluid and isotropic formulations that have been widely studied as delivery systems for a variety of routes, including the skin. In spite of what the name suggests, microemulsions are nanocarriers, and their use as topical delivery systems derives from their multiple advantages compared to other dermatological formulations, such as ease of preparation, thermodynamic stability and penetration-enhancing properties. Composition, charge and internal structure have been reported as determinant factors for the modulation of drug release and cutaneous and transdermal transport. This manuscript aims at reviewing how these and other characteristics affect delivery and make microemulsions appealing for topical and transdermal administration, as well as how they can be modulated during the formulation design to improve the potential and efficacy of the final system. Full article
(This article belongs to the Special Issue Advanced Transdermal Drug Delivery)
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Open AccessReview Hollow Pollen Shells to Enhance Drug Delivery
Pharmaceutics 2014, 6(1), 80-96; doi:10.3390/pharmaceutics6010080
Received: 24 January 2014 / Revised: 5 March 2014 / Accepted: 6 March 2014 / Published: 14 March 2014
Cited by 15 | PDF Full-text (2069 KB) | HTML Full-text | XML Full-text
Abstract
Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly
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Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell. Full article
(This article belongs to the Special Issue Microencapsulation Technology Applied to Pharmaceutics 2014)
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Open AccessReview Application of Pharmacokinetic and Pharmacodynamic Analysis to the Development of Liposomal Formulations for Oncology
Pharmaceutics 2014, 6(1), 137-174; doi:10.3390/pharmaceutics6010137
Received: 14 January 2014 / Revised: 22 February 2014 / Accepted: 26 February 2014 / Published: 18 March 2014
Cited by 14 | PDF Full-text (1169 KB) | HTML Full-text | XML Full-text
Abstract
Liposomal formulations of anticancer agents have been developed to prolong drug circulating lifetime, enhance anti-tumor efficacy by increasing tumor drug deposition, and reduce drug toxicity by avoiding critical normal tissues. Despite the clinical approval of numerous liposome-based chemotherapeutics, challenges remain in the development
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Liposomal formulations of anticancer agents have been developed to prolong drug circulating lifetime, enhance anti-tumor efficacy by increasing tumor drug deposition, and reduce drug toxicity by avoiding critical normal tissues. Despite the clinical approval of numerous liposome-based chemotherapeutics, challenges remain in the development and clinical deployment of micro- and nano-particulate formulations, as well as combining these novel agents with conventional drugs and standard-of-care therapies. Factors requiring optimization include control of drug biodistribution, release rates of the encapsulated drug, and uptake by target cells. Quantitative mathematical modeling of formulation performance can provide an important tool for understanding drug transport, uptake, and disposition processes, as well as their role in therapeutic outcomes. This review identifies several relevant pharmacokinetic/pharmacodynamic models that incorporate key physical, biochemical, and physiological processes involved in delivery of oncology drugs by liposomal formulations. They capture observed data, lend insight into factors determining overall antitumor response, and in some cases, predict conditions for optimizing chemotherapy combinations that include nanoparticulate drug carriers. Full article
(This article belongs to the Special Issue Liposome Technologies)
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Other

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Open AccessConcept Paper An Evaluation of Intranasal Sufentanil and Dexmedetomidine for Pediatric Dental Sedation
Pharmaceutics 2014, 6(1), 175-184; doi:10.3390/pharmaceutics6010175
Received: 5 November 2013 / Revised: 22 January 2014 / Accepted: 13 February 2014 / Published: 21 March 2014
Cited by 6 | PDF Full-text (245 KB) | HTML Full-text | XML Full-text
Abstract
Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal
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Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX) has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal (IN) midazolam, IN application of DEX and sufentanil (SUF) does not appear to cause much discomfort. Further, although DEX lacks respiratory depressive effects, it is an α2-agonist that can cause hypotension and bradycardia when given in high doses or during prolonged periods of administration. The aim of this feasibility study was to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric dental procedures. After IRB approval and informed consent, children (aged 3–7 years; n = 20) from our dental clinic were recruited. All patients received 2 μg/kg (max 40 μg) of IN DEX 45 min before the procedure, followed 30 min later by 1 μg/kg (max 20 μg) of IN SUF. An independent observer rated the effects of sedation using the Ohio State University Behavior Rating Scale (OSUBRS) and University of Michigan Sedation Scale (UMSS). The dentist and the parent also assessed the efficacy of sedation. Dental procedures were well tolerated and none were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score was 1.6, and all scores returned to baseline after the procedure. The average dentist rated quality of sedation was 7.6 across the 20 subjects. After discharge, parents reported one child with prolonged drowsiness and one child who vomited at home. The use of IN DEX supplemented with IN SUF provided both an effective and tolerable form of moderate sedation. Although onset and recovery are slower than with oral (PO) midazolam and transmucosal fentanyl, the quality of the sedation may be better with less risk of respiratory depression. Results from this preliminary study showed no major complications from IN delivery of these agents. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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