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Pharmaceutics, Volume 9, Issue 2 (June 2017)

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Cover Story This artwork depicts the use of poly(styrene-co-maleic-anhydride) (SMA) conjugated folic acid (FA) [...] Read more.
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Research

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Open AccessArticle Blend Hydrogel Microspheres of Carboxymethyl Chitosan and Gelatin for the Controlled Release of 5-Fluorouracil
Pharmaceutics 2017, 9(2), 13; doi:10.3390/pharmaceutics9020013
Received: 26 September 2016 / Revised: 10 February 2017 / Accepted: 10 February 2017 / Published: 27 March 2017
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Abstract
Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH
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Carboxymethyl chitosan (CMCS) was synthesized and blended with gelatin (GE) to prepare hydrogel microspheres by w/o emulsion cross-linking in the presence of glutaraldehyde (GA), which acted as a cross-linker. 5-Fluorouracil (5-FU) was encapsulated to investigate its controlled release (CR) characteristics in acidic (pH 1.2) and alkaline (pH 7.4) buffer media. The microspheres which formed were spherical in nature, with smooth surfaces, as judged by the scanning electron microscopy (SEM). Fourier transform infrared spectroscopy (FTIR) confirmed the carboxymethylation of CS and the chemical stability of 5-FU in the formulations. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the physical state and molecular level dispersion of 5-FU. Equilibrium swelling of microspheres was performed in water, in order to understand the water uptake properties. The in vitro release of 5-FU was extended up to 12 h in pH 7.4 phosphate buffer, revealing an encapsulation efficiency of 72%. The effects of blend composition, the extent of cross-linking, and initial drug loading on the in vitro release properties, were investigated. When analyzed through empirical equations, the release data suggested a non-Fickian transport mechanism. Full article
(This article belongs to the Special Issue Nanotechnology in Medical Therapeutic Formulations)
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Open AccessArticle Folate Decorated Nanomicelles Loaded with a Potent Curcumin Analogue for Targeting Retinoblastoma
Pharmaceutics 2017, 9(2), 15; doi:10.3390/pharmaceutics9020015
Received: 28 March 2017 / Revised: 11 April 2017 / Accepted: 11 April 2017 / Published: 18 April 2017
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Abstract
The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability
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The aim of this study was to develop a novel folate receptor-targeted drug delivery system for retinoblastoma cells using a promising anticancer agent, curcumin-difluorinated (CDF), loaded in polymeric micelles. Folic acid was used as a targeting moiety to enhance the targeting and bioavailability of CDF. For this purpose, amphiphilic poly(styrene-co-maleic acid)-conjugated-folic acid (SMA-FA) was synthesized and utilized to improve the aqueous solubility of a highly hydrophobic, but very potent anticancer compound, CDF, and its targeted delivery to folate overexpressing cancers. The SMA-FA conjugate was first synthesized and characterized by 1H NMR, FTIR and DSC. Furthermore, the chromatographic condition (HPLC) for estimating CDF was determined and validated. The formulation was optimized to achieve maximum entrapment of CDF. The particle size of the micelles was measured and confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cytotoxicity studies were conducted on (Y-79 and WERI-RB) retinoblastoma cells. Results showed that the solubility of CDF could be increased with the newly-synthesized polymer, and the entrapment efficiency was >85%. The drug-loaded nanomicelles exhibited an appropriate size of <200 nm and a narrow size distribution. The formulation did not show any adverse cytotoxicity on a human retinal pigment epithelial cell (ARPE-19), indicating its safety. However, it showed significant cell killing activity in both Y-79 and WERI-RB retinoblastoma cell lines, indicating its potency in killing cancer cells. In conclusion, the folic acid-conjugated SMA loaded with CDF showed promising potential with high safety and pronounced anticancer activity on the tested retinoblastoma cell lines. The newly-formulated targeted nanomicelles thus could be a viable option as an alternative approach to current retinoblastoma therapies. Full article
(This article belongs to the Special Issue Nanotechnology Advances in Cancer Treatment)
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Open AccessArticle Accessing Mefenamic Acid Form II through High-Pressure Recrystallisation
Pharmaceutics 2017, 9(2), 16; doi:10.3390/pharmaceutics9020016
Received: 6 March 2017 / Revised: 4 May 2017 / Accepted: 10 May 2017 / Published: 16 May 2017
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Abstract
High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by
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High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using a diamond anvil cell. A comparison of the crystal structures shows that the efficient packing of molecules in Form II was enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in a 14% decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which was confirmed by the results of crystallisation at high pressure. Full article
(This article belongs to the Special Issue Selected papers from 7th APS International PharmSci Conference)
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Open AccessArticle Optimizing Prednisolone Loading into Distiller’s Dried Grain Kafirin Microparticles, and In vitro Release for Oral Delivery
Pharmaceutics 2017, 9(2), 17; doi:10.3390/pharmaceutics9020017
Received: 10 March 2017 / Revised: 20 April 2017 / Accepted: 2 May 2017 / Published: 19 May 2017
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Abstract
Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery
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Kafirin microparticles have potential as colon-targeted delivery systems because of their ability to protect encapsulated material from digestive processes of the upper gastrointestinal tract (GIT). The aim was to optimize prednisolone loading into kafirin microparticles, and investigate their potential as an oral delivery system. Response surface methodology (RSM) was used to predict the optimal formulation of prednisolone loaded microparticles. Prednisolone release from the microparticles was measured in simulated conditions of the GIT. The RSM models were inadequate for predicting the relationship between starting quantities of kafirin and prednisolone, and prednisolone loading into microparticles. Compared to prednisolone released in the simulated gastric and small intestinal conditions, no additional drug release was observed in simulated colonic conditions. Hence, more insight into factors affecting drug loading into kafirin microparticles is required to improve the robustness of the RSM model. This present method of formulating prednisolone-loaded kafirin microparticles is unlikely to offer clinical benefits over commercially available dosage forms. Nevertheless, the overall amount of prednisolone released from the kafirin microparticles in conditions simulating the human GIT demonstrates their ability to prevent the release of entrapped core material. Further work developing the formulation methods may result in a delivery system that targets the lower GIT. Full article
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Open AccessArticle Quality Attributes and In Vitro Bioequivalence of Different Brands of Amoxicillin Trihydrate Tablets
Pharmaceutics 2017, 9(2), 18; doi:10.3390/pharmaceutics9020018
Received: 3 April 2017 / Revised: 3 May 2017 / Accepted: 16 May 2017 / Published: 20 May 2017
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Abstract
Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes,
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Bacterial resistance and antibiotic drug effectiveness can be related to administering generic products with a subtherapeutic dose or poor in vivo drug release. The aim of this study was to investigate whether locally marketed amoxicillin tablets have the required chemical and physical attributes, including in vitro bioequivalence performance. Five generic products (T1, T2, T3, T4, and T5) containing combination of amoxicillin trihydrate and potassium clavulanate as 1 g strength present in immediate release tablets were compared to the reference listed drug product Augmentin® (R) for weight variation, friability, resistance to crushing, and chemical content of amoxicillin. Difference (ƒ1) and similarity (ƒ2) factors were calculated to assess in vitro bioequivalence requirements. The tablets from different products have shown compliance with the pharmacopeial requirements of the performed tests. The measured resistance to crushing of tablets did not influence the dissolution time. Three generic products released more than 85% of amoxicillin by the first 15 min as did the reference product and were considered as bioequivalent products. T1 and T4 had ƒ1 values of 16.5% and 25.4% respectively and their ƒ2 values were 44.5 and 34.6 respectively, indicating failure to meet in vitro bioequivalence requirements. Tablet formulations can play an important role in achieving bioequivalence. Independent investigations such as this study serve as an important tool to reveal possible inferior or noncompliant products that may find their way to the market. Full article
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Open AccessArticle Stability Study of Sunscreens with Free and Encapsulated UV Filters Contained in Plastic Packaging
Pharmaceutics 2017, 9(2), 19; doi:10.3390/pharmaceutics9020019
Received: 2 January 2017 / Revised: 10 April 2017 / Accepted: 24 May 2017 / Published: 31 May 2017
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Abstract
Sunscreens play a fundamental role in skin cancer prevention and in protection against photo-aging. UV filters are often photo-unstable, especially in relation to their vehicles and, being lipophilic substances, they are able to interact with plastic packaging. Finally, UV filter stability can be
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Sunscreens play a fundamental role in skin cancer prevention and in protection against photo-aging. UV filters are often photo-unstable, especially in relation to their vehicles and, being lipophilic substances, they are able to interact with plastic packaging. Finally, UV filter stability can be significantly affected by the routine use of the product at high temperatures. This work aims to study the stability of sunscreen formulations in polyethylene packaging. Butyl methoxydibenzoylmethane and octocrylene, both in a free form and as encapsulated filters were chosen as UV filters. Stability evaluations were performed both in the packaging and on the formulations. Moreover, a further two non-destructive techniques, near-infrared (NIR) spectroscopy and a multiple light scattering technique, were also used to evaluate the stability of the formulation. Results demonstrated clearly that all of the pack underwent significant changes in its elastic/plastic behavior and in external color after solar irradiation. From the evaluation of the extractable profile of untreated and treated packaging material an absorption of 2-phenoxyethanol and octocrylene were shown. In conclusion, the results highlighted clearly that a reduction of the UV filter in the formulation packed in high-density polyethylene/low-density polyethylene (HDPE/LDPE) material can occur over time, reducing the protective effect of the product when applied to the skin. Full article
(This article belongs to the Special Issue Drug Stability)
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Open AccessArticle An Evaluation of the Binding Strength of Okra Gum and the Drug Release Characteristics of Tablets Prepared from It
Pharmaceutics 2017, 9(2), 20; doi:10.3390/pharmaceutics9020020
Received: 16 March 2017 / Revised: 15 May 2017 / Accepted: 24 May 2017 / Published: 2 June 2017
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Abstract
The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was
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The aim of this study is to evaluate the adhesion ability of okra gum, which is gaining popularity as a tablet binder. For this purpose, gum was extracted from okra pods, and the binding strength of different concentrations (1%, 3%, and 5%) was determined quantitatively. Additionally, naproxen sodium tablets were prepared by using okra gum as a binder and were evaluated for their properties including hardness, friability, disintegration time, and dissolution rate. The binding strength values were compared with that of pre-gelatinized starch, a commonly used tablet binder. The results from universal testing machine indicate that the binding strengths of all dispersions of okra increase as the concentration increases from 1% to 5% and ranges from 2.5 to 4.5 N, which are almost twice a high as those of pre-gelatinized starch. The tablets prepared with okra gum have shown good mechanical strength with hardness values of 7–8.5 kg/cm2 and a friability <1%, comparable to tablets prepared with starch. The disintegration time was longer (7.50 min with okra gum and 5.05 min with starch paste), and the drug release from these tablets was slower than the formulations with starch. The higher binding ability of okra gum probably linked with its chemical composition as it mainly contains galactose, rhamnose, and galacturonic acid. This study concludes that okra gum is a better binder than pre-gelatinized starch, it might be explored in future for introduction as a cost-effective binder in the pharmaceutical industry. Full article
(This article belongs to the Special Issue Selected papers from 7th APS International PharmSci Conference)
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Open AccessArticle Surface-Modification of Carbonate Apatite Nanoparticles Enhances Delivery and Cytotoxicity of Gemcitabine and Anastrozole in Breast Cancer Cells
Pharmaceutics 2017, 9(2), 21; doi:10.3390/pharmaceutics9020021
Received: 16 February 2017 / Revised: 20 April 2017 / Accepted: 24 April 2017 / Published: 7 June 2017
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Abstract
pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer
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pH sensitive nanoparticles of carbonate apatite (CA) have been proven to be effective delivery vehicles for DNA, siRNAs and proteins. More recently, conventional anti-cancer drugs, such as doxorubicin, methotrexate and cyclophosphamide have been successfully incorporated into CA for intracellular delivery to breast cancer cells. However, physical and chemical properties of drug molecules appeared to affect their interactions with CA, with hydrophillic drug so far exhibiting better binding affinity and cellular uptakes compared to hydrophobic drugs. In this study, anastrozole, a non-steroidal aromatase inhibitor which is largely hydrophobic, and gemcitabine, a hydrophilic nucleoside inhibitor were used as solubility models of chemotherapy drug. Aggregation tendency of poorly soluble drugs resulting in larger particle-drug complex size might be the main factor hindering their delivery effectiveness. For the first time, surface modification of CA with poly(ethylene glycol) (PEG) has shown promising result to drastically reduce anastrozole- loaded CA particle size, from approximately 1000 to 500 nm based on zeta sizer analysis. Besides PEG, a cell specific ligand, in this case fibronectin, was attached to the particles in order to facilitate receptor mediated endocytosis based on fibronectin–integrin interaction. High-performance liquid chromatography (HPLC) was performed to measure uptake of the drugs by breast cancer cells, revealing that surface modification increased the drug uptake, especially for the hydrophobic drug, compared to the uncoated particles and the free drug. In vitro chemosensitivity assay and in vivo tumor regression study also showed that coated apatite/drug nanoparticle complexes presented higher cytotoxicity and tumor regression effects than uncoated apatite/drug nanoparticles and free drugs, indicating that surface modification successfully created optimum particles size with the consequence of more effective uptake along with favorable pharmacokinetics of the particles. Full article
(This article belongs to the Special Issue Nanotechnology in Medical Therapeutic Formulations)
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Review

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Open AccessReview Liposomal Formulations in Clinical Use: An Updated Review
Pharmaceutics 2017, 9(2), 12; doi:10.3390/pharmaceutics9020012
Received: 16 January 2017 / Revised: 20 March 2017 / Accepted: 23 March 2017 / Published: 27 March 2017
Cited by 13 | PDF Full-text (2339 KB) | HTML Full-text | XML Full-text
Abstract
Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their
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Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes. Full article
(This article belongs to the Special Issue Nanotechnology in Medical Therapeutic Formulations)
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Open AccessReview What Does It “Mean”? A Review of Interpreting and Calculating Different Types of Means and Standard Deviations
Pharmaceutics 2017, 9(2), 14; doi:10.3390/pharmaceutics9020014
Received: 17 January 2017 / Revised: 31 March 2017 / Accepted: 5 April 2017 / Published: 13 April 2017
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Abstract
Typically, investigations are conducted with the goal of generating inferences about a population (humans or animal). Since it is not feasible to evaluate the entire population, the study is conducted using a randomly selected subset of that population. With the goal of using
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Typically, investigations are conducted with the goal of generating inferences about a population (humans or animal). Since it is not feasible to evaluate the entire population, the study is conducted using a randomly selected subset of that population. With the goal of using the results generated from that sample to provide inferences about the true population, it is important to consider the properties of the population distribution and how well they are represented by the sample (the subset of values). Consistent with that study objective, it is necessary to identify and use the most appropriate set of summary statistics to describe the study results. Inherent in that choice is the need to identify the specific question being asked and the assumptions associated with the data analysis. The estimate of a “mean” value is an example of a summary statistic that is sometimes reported without adequate consideration as to its implications or the underlying assumptions associated with the data being evaluated. When ignoring these critical considerations, the method of calculating the variance may be inconsistent with the type of mean being reported. Furthermore, there can be confusion about why a single set of values may be represented by summary statistics that differ across published reports. In an effort to remedy some of this confusion, this manuscript describes the basis for selecting among various ways of representing the mean of a sample, their corresponding methods of calculation, and the appropriate methods for estimating their standard deviations. Full article
(This article belongs to the Special Issue Veterinary Medicine)
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