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Pharmaceutics, Volume 6, Issue 2 (June 2014), Pages 195-353

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Research

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Open AccessArticle Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses
Pharmaceutics 2014, 6(2), 220-234; doi:10.3390/pharmaceutics6020220
Received: 14 February 2014 / Revised: 21 April 2014 / Accepted: 25 April 2014 / Published: 15 May 2014
Cited by 5 | PDF Full-text (720 KB) | HTML Full-text | XML Full-text
Abstract
This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. [...] Read more.
This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables. Full article
(This article belongs to the Special Issue Advanced Transdermal Drug Delivery)
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Open AccessArticle Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles
Pharmaceutics 2014, 6(2), 235-248; doi:10.3390/pharmaceutics6020235
Received: 3 April 2014 / Revised: 8 May 2014 / Accepted: 9 May 2014 / Published: 22 May 2014
Cited by 7 | PDF Full-text (926 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The synthesis method of layered double hydroxides (LDHs) determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. [...] Read more.
The synthesis method of layered double hydroxides (LDHs) determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen) using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h). After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties. Full article
(This article belongs to the Special Issue Layered Double Hydroxide Used in Drug Delivery)
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Open AccessArticle Preliminary Studies on Validation of Calu-3 Cell Line as a Model for Screening Respiratory Mucosa Irritation and Toxicity
Pharmaceutics 2014, 6(2), 268-280; doi:10.3390/pharmaceutics6020268
Received: 26 January 2014 / Revised: 29 May 2014 / Accepted: 3 June 2014 / Published: 13 June 2014
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Abstract
There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of [...] Read more.
There is need to develop reproducible methods and experimental models for screening mucosal irritation and toxicity for drugs and pharmaceutical excipients. The aim of this study was to validate Calu-3 cell line as a model for screening respiratory irritation and toxicity of drugs and excipients. Eighteen test compounds were selected according to their irritation potential and European Centre for the Validation of Alternative Methods (ECVAM) guidelines. Cell toxicity and irritation was determined using MTT assay. Data analysis and interpretation were done using modified ECVAM approach; where replicate values met acceptance criteria if percent relative standard deviation (RSD) of the raw data is <18%. Compounds with mean relative viability values of 50% and below were classified as irritant (I); those above 50% were non-irritant (NI). At low concentration (0.2% w/v) and 1 h incubation, the Calu-3 cell culture model accurately predicted the toxicity of most test compounds. The specificity of our proposed model (percentage of in vivo non-irritants correctly predicted), concordance (percentage of compounds correctly predicted) and sensitivity (percentage of in vivo irritants correctly predicted) at 0.2% w/v and 60 min exposure were 100%, 72%, and 44%, respectively. In conclusion, the Calu-3 cell line in conjunction with MTT assay appears to be a potentially useful tool for screening drugs and excipients for respiratory mucosa irritation and toxicity. However, as the data reported in this study were solely based on MTT assay, additional studies are needed using other toxicity-/irritation-indicating methods to confirm the observed trend. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessArticle Development of Multilayer Microcapsules by a Phase Coacervation Method Based on Ionic Interactions for Textile Applications
Pharmaceutics 2014, 6(2), 281-297; doi:10.3390/pharmaceutics6020281
Received: 21 January 2014 / Revised: 9 May 2014 / Accepted: 20 May 2014 / Published: 13 June 2014
Cited by 5 | PDF Full-text (1220 KB) | HTML Full-text | XML Full-text
Abstract
The present study describes the development of multilayer microcapsules by 11 alternate additions of chitosan (Chi) and sodium dodecyl sulfate (SDS) in a combined emulsification and phase coacervation method based on ionic interactions. After an alkali treatment, microcapsules are applied on polyester [...] Read more.
The present study describes the development of multilayer microcapsules by 11 alternate additions of chitosan (Chi) and sodium dodecyl sulfate (SDS) in a combined emulsification and phase coacervation method based on ionic interactions. After an alkali treatment, microcapsules are applied on polyester (PET) fabric by a padding process to investigate their wash-durability on fabric. Air atmospheric plasma treatment is performed on PET fabric to modify the surface properties of the textiles. Zeta potential, X-ray photoelectron spectroscopy (XPS), wetting measurements, scanning electron microscopy (SEM), and atomic force microscopy (AFM) with surface roughness measurements are realized to characterize and determine wash durability of microcapsule samples onto PET. After alkali treatment, the microcapsules are selected for textile application because they are submicron sized with the desired morphology. The results obtained from various characterization techniques indicate that microcapsules are wash-durable on PET fabric pre activated by air plasma atmospheric as Chi based microcapsules can interact directly with PET by ionic interactions. 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 Analytical Challenges and Regulatory Requirements for Nasal Drug Products in Europe and the U.S.
Pharmaceutics 2014, 6(2), 195-219; doi:10.3390/pharmaceutics6020195
Received: 20 December 2013 / Revised: 24 March 2014 / Accepted: 31 March 2014 / Published: 11 April 2014
Cited by 2 | PDF Full-text (5473 KB) | HTML Full-text | XML Full-text
Abstract
Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the [...] Read more.
Nasal drug delivery can be assessed by a variety of means and regulatory agencies, e.g., the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have published a set of guidelines and regulations proposing in vitro test methods for the characterization of nasal drug products. This article gives a summary of the FDA and EMA requirements regarding the determination of droplet size distribution (DSD), plume geometry, spray pattern and shot weights of solution nasal sprays and discusses the analytical challenges that can occur when performing these measurements. In order to support findings from the literature, studies were performed using a standard nasal spray pump and aqueous model formulations. The aim was to identify possible method-, device- and formulation-dependent influencing factors. The literature review, as well as the results from the studies show that DSD, plume geometry and spray pattern are influenced by, e.g., the viscosity of the solution, the design of the device and the actuation parameters, particularly the stroke length, actuation velocity and actuation force. The dominant factor influencing shot weights, however, is the adjustment of the actuation parameters, especially stroke length and actuation velocity. Consequently, for routine measurements assuring, e.g., the quality of a solution nasal spray or, for in vitro bioequivalence studies, the critical parameters, have to be identified and considered in method development in order to obtain reproducible and reliable results. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessReview Drug-Eluting Nasal Implants: Formulation, Characterization, Clinical Applications and Challenges
Pharmaceutics 2014, 6(2), 249-267; doi:10.3390/pharmaceutics6020249
Received: 26 January 2014 / Revised: 28 March 2014 / Accepted: 7 May 2014 / Published: 27 May 2014
Cited by 1 | PDF Full-text (582 KB) | HTML Full-text | XML Full-text
Abstract
Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as [...] Read more.
Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable alternatives for addressing these concerns. This article reviewed potential drug candidates for nasal implants, formulation methods/optimization and characterization methods. Clinical applications and important considerations were also addressed. Clinically-approved implants (Propel™ implant, the Relieva stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) for CRS treatment was an important focus. The advantages and limitations, as well as future considerations, challenges and the need for additional research in the field of nasal drug implant development, were discussed. Full article
(This article belongs to the Special Issue Respiratory and Nasal Drug Delivery)
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Open AccessReview Layered Double Hydroxide-Based Nanocarriers for Drug Delivery
Pharmaceutics 2014, 6(2), 298-332; doi:10.3390/pharmaceutics6020298
Received: 11 April 2014 / Revised: 15 May 2014 / Accepted: 20 May 2014 / Published: 17 June 2014
Cited by 16 | PDF Full-text (2325 KB) | HTML Full-text | XML Full-text
Abstract
Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to [...] Read more.
Biocompatible clay materials have attracted particular attention as the efficient drug delivery systems (DDS). In this article, we review developments in the use of layered double hydroxides (LDHs) for controlled drug release and delivery. We show how advances in the ability to synthesize intercalated structures have a significant influence on the development of new applications of these materials. We also show how modification and/or functionalization can lead to new biotechnological and biomedical applications. This review highlights the most recent progresses in research on LDH-based controlled drug delivery systems, focusing mainly on: (i) DDS with cardiovascular drugs as guests; (ii) DDS with anti-inflammatory drugs as guests; and (iii) DDS with anti-cancer drugs as guests. Finally, future prospects for LDH-based drug carriers are also discussed. Full article
(This article belongs to the Special Issue Layered Double Hydroxide Used in Drug Delivery)
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Open AccessReview Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers
Pharmaceutics 2014, 6(2), 333-353; doi:10.3390/pharmaceutics6020333
Received: 4 March 2014 / Revised: 25 April 2014 / Accepted: 4 June 2014 / Published: 20 June 2014
Cited by 6 | PDF Full-text (1292 KB) | HTML Full-text | XML Full-text
Abstract
Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory [...] Read more.
Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEG)ylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols. Full article
(This article belongs to the Special Issue Liposome Technologies)
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