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Pharmaceutical Research
Journal Prestige (SJR): 1.077
Citation Impact (citeScore): 3
Number of Followers: 161  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-904X - ISSN (Online) 0724-8741
Published by Springer-Verlag Homepage  [2351 journals]
  • Correction to: Pharmacokinetic and Tissue Distribution Profile of Long
           Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in
           Humanized Mice Model
    • Abstract: There are errors in the published article (Volume 34, Number 12, pp. 2749–2755). The errors occurred in pharmacokinetic study design of materials and methods section on page 2750–51.
      PubDate: 2019-05-20
       
  • Investigating the Influence of Polysorbate 20/80 and Polaxomer P188 on the
           
    • Abstract: Purpose To provide new insights into how protein-surfactant competitive adsorbtion and corresponding surface tension reduction properties at the air-water and oil-water interface are impacted by the type of protein and the associated protein surface rheology. Method Interfacial Rheology was utilized to obtain surface G’ and G” as a function of frequency. Force tensiometry was utilized to obtain changes in surface tension as a function of surfactant concentration. The impact on surface properties of two different proteins i.e. BSA and Lysozyme was investigated as a function of surfactant concentration i.e. polysorbates PS 20, PS 80 and Poloxomer (Kolliphor P188). Results Surface tension and interfacial tension measurements for BSA showed that in mixed BSA/polysorbate surfactant systems, BSA dominates the interfacial behavior at both the air-water and oil-water interfaces, until a high polysorbate concentration of 0.1 mg/ml. At these high polysorbate concentrations a mixed BSA-Polysorbate interfacial layer is formed as corroborated by the surface elasticity values being lower than that of pure BSA but higher than that of pure Polysorbate. For Kolliphor, it was observed that Kolliphor was unable to displace BSA at any concentration. This is corroborated by the high surface elasticity of the BSA which is maintained in the presence of Kolliphor. Surface and interfacial tension measurements for lysozyme show that for mixed lysozyme/polysorbate surfactant systems, the surface tension values are lower than that exhibited by either the lysozyme or the polysorbate surfactants. This potentially indicates the formation of a mixed layer of lysozyme and polysorbate. At the high polysorbate concentrations probed, the surface elasticity values are however closer to that of pure polysorbates, indicating that the mixed layer may be more heavily polysorbate dominated, especially at high polysorbate concentrations. For Kolliphor, the response was similar to that seen in the Kolliphor-BSA system in which the Kolliphor was not able to displace the protein i.e. Lysozyme. Conclusions In conclusion, it was seen that competitive adsorption between proteins and common excipient surfactants is dictated by the type of protein and its effective structuring/rigidity at the surface as reflected through surface elasticity and surface tan delta values. BSA was seen to exhibit a higher surface elasticity than lysozyme, and therefore has a more rigid structure and is more competitive at the interface.
      PubDate: 2019-05-20
       
  • Correction to: Evaluation of Wound Healing Potential of β-Chitin
           Hydrogel/Nano Zinc Oxide Composite Bandage
    • Abstract: In the original manuscript, the platelet activation images of the sample treated groups, Fig. 3c were provided incorrectly.
      PubDate: 2019-05-17
       
  • The Natural Product Eugenol Is an Inhibitor of the Ebola Virus In Vitro
    • Abstract: Purpose Since the 2014 Ebola virus (EBOV) outbreak in West Africa there has been considerable effort towards developing drugs to treat Ebola virus disease and yet to date there is no FDA approved treatment. This is important as at the time of writing this manuscript there is an ongoing outbreak in the Democratic Republic of the Congo which has killed over 1000. Methods We have evaluated a small number of natural products, some of which had shown antiviral activity against other pathogens. This is exemplified with eugenol, which is found in high concentrations in multiple essential oils, and has shown antiviral activity against feline calicivirus, tomato yellow leaf curl virus, Influenza A virus, Herpes Simplex virus type 1 and 2, and four airborne phages. Results Four compounds possessed EC50 values less than or equal to 11 μM. Of these, eugenol, had an EC50 of 1.3 μM against EBOV and is present in several plants including clove, cinnamon, basil and bay. Eugenol is much smaller and structurally unlike any compound that has been previously identified as an inhibitor of EBOV, therefore it may provide new mechanistic insights. Conclusion This compound is readily accessible in bulk quantities, is inexpensive, and has a long history of human consumption, which endorses the idea for further assessment as an antiviral therapeutic. This work also suggests that a more exhaustive assessment of natural product libraries against EBOV and other viruses is warranted to improve our ability to identify compounds that are so distinct from FDA approved drugs.
      PubDate: 2019-05-17
       
  • Differentiating the Effects of Oxidative Stress Tests on
           Biopharmaceuticals
    • Abstract: Purpose A rapid and broadly applicable method to assess relevant oxidative damage in biopharmaceuticals is important for lifecycle management of product quality. Multiple methods are currently employed as stress tests to induce oxidative damage for assessment of stability, safety, and efficacy. We compared two common methods for inducing oxidative damage to assess differences in impact on bioactivity and structure of the biopharmaceuticals. Methods Biopharmaceuticals were treated with either metal-catalyzed oxidation (MCO) conditions or the reactive-oxygen species (ROS) inducer 2,2′-Azobis(2-amidinopropane) dihydrochloride (AAPH), then analyzed for changes in structure and bioactivity. Results We demonstrate that commonly used chemical methods for assessing oxidation yield distinct oxidation profiles for each of the biotechnology products analyzed, including monoclonal antibodies. We further report oxidant- and product-specific changes in bioactivity under oxidizing conditions, along with differential oxidation on the molecular subunits of monoclonal antibodies. Conclusion Our results highlight the need for product-specific optimization and selection of orthogonal, relevant oxidizers when characterizing stress responses in biopharmaceuticals.
      PubDate: 2019-05-17
       
  • A Single Hydrogen to Fluorine Substitution Reverses the Trend of Surface
           Composition Enrichment of Sorafenib Amorphous Solid Dispersion upon
           Moisture Exposure
    • Abstract: Purpose To reveal the underlying mechanism inducing the opposite trends of surface composition enrichment of spray dried amorphous solid dispersions (ASD) of sorafenib and regorafenib, two compounds only differ in hydrogen to fluorine substitution. Methods Sorafenib/PVP and regorafenib/PVP ASDs were prepared by spray drying. Morphology of ASDs was visually inspected and examined by SEM. The surface compositions of ASDs were analyzed by XPS. Glass transition temperature (Tg) of ASDs was determined by DSC. Water vapor sorption isotherms of ASDs were studied by moisture sorption analyzer. Molecular interaction between the drug and the polymer was analyzed by solution NMR. Results In 10% and 20% drug loading sorafenib/PVP ASDs, short time moisture exposure induced PVP enrichment on the surface, and the appearance of initial ASDs powder became gel-like after water uptake. While in 30% sorafenib/PVP and any regorafenib/PVP ASDs regardless of drug loading, moisture exposure induced surface drug enrichment, while their powder-like appearance and average particle size remained unchanged. Meanwhile, sorafenib/PVP had similar water vapor sorption isotherms as regorafenib/PVP, before and after moisture induced phase separation. NMR study demonstrated a hex atomic ring H-bonding interaction between the drug and PVP, with a 1:1 drug: monomer stoichiometry molar ratio, which persisted in sorafenib/PVP but not regorafenib/PVP system under 95%RH moisture. Conclusions Moisture exposure could lead to drug or polymer enrichment on the surface of ASDs, while the viability of drug-polymer interaction persisting in water environment contributed to such surface composition enrichment.
      PubDate: 2019-05-17
       
  • A Proof of Concept for 3D Printing of Solid Lipid-Based Formulations of
           Poorly Water-Soluble Drugs to Control Formulation Dispersion Kinetics
    • Abstract: Purpose The use of three-dimensional printing (3DP) in the development of pharmaceutical dosage forms is growing rapidly. However, the research is almost exclusively focussed on polymer-based systems with very little reported on 3D printing of lipid-based formulations. Thus, the aim of the work was to explore the feasibility of 3DP technology to prepare solid lipid-based formulations. Here, 3DP was applied for the preparation of solid self-microemulsifying drug delivery systems (S-SMEDDS) with defined surface area to volume (SA/V) ratios. Methods The S-SMEDDS formulations, comprised of Gelucire® 44/14, Gelucire® 48/16 and Kolliphor® P 188 were loaded with fenofibrate or cinnarizine as model drugs. The formulations were printed into four geometrical shapes - cylindrical, prism, cube and torus, and compared to a control cube manually prepared from bulk formulation. Results The printing process was not significantly affected by the presence of the model drugs. The as-printed S-SMEDDS formulations were characterised using differential scanning calorimetry and wide-angle X-ray scattering. The kinetics of dispersion depended on the SA/V ratio values. The digestion process was affected by the initial geometry of the dosage form by virtue of the kinetics of dispersion of the dosage forms into the digestion medium. Conclusions This proof of concept study has demonstrated the potential of 3DP for the development of customised S-SMEDDS formulations without the need for an additional carrier or additive and with optimisation could elaborate a new class of dosage forms based on 3D printed lipids. Graphical abstract Lipid based formulations were 3D printed in various shapes to control the surface are to volume ratio and consequently the kinetics of dispersion
      PubDate: 2019-05-16
       
  • Characterization of Plasma Membrane Localization and Phosphorylation
           Status of Organic Anion Transporting Polypeptide (OATP) 1B1 c.521 T>C
           Nonsynonymous Single-Nucleotide Polymorphism
    • Abstract: Purpose Membrane transport protein organic anion transporting polypeptide (OATP) 1B1 mediates hepatic uptake of many drugs (e.g. statins). The OATP1B1 c.521 T > C (p. V174A) polymorphism has reduced transport activity. Conflicting in vitro results exist regarding whether V174A-OATP1B1 has reduced plasma membrane localization; no such data has been reported in physiologically relevant human liver tissue. Other potential changes, such as phosphorylation, of the V174A-OATP1B1 protein have not been explored. Current studies characterized the plasma membrane localization of V174A-OATP1B1 in genotyped human liver tissue and cell culture and compared the phosphorylation status of V174A- and wild-type (WT)-OATP1B1. Methods Localization of V174A- and WT-OATP1B1 were determined in OATP1B1 c.521 T > C genotyped human liver tissue (n = 79) by immunohistochemistry and in transporter-overexpressing human embryonic kidney (HEK) 293 and HeLa cells by surface biotinylation and confocal microscopy. Phosphorylation and transport of OATP1B1 was determined using 32P-orthophosphate labeling and [3H]estradiol-17β-glucuronide accumulation, respectively. Results All three methods demonstrated predominant plasma membrane localization of both V174A- and WT-OATP1B1 in human liver tissue and in cell culture. Compared to WT-OATP1B1, the V174A-OATP1B1 has significantly increased phosphorylation and reduced transport. Conclusions We report novel findings of increased phosphorylation, but not impaired membrane localization, in association with the reduced transport function of the V174A-OATP1B1.
      PubDate: 2019-05-15
       
  • Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of
           Spray-Drying Kinetics with Inhalable Pharmaceutics
    • Abstract: Purpose Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.
      PubDate: 2019-05-14
       
  • Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid)
           Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery
    • Abstract: Purpose To design and stabilize Liraglutide loaded poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) proper for oral administration. Methods PLGA NPs were prepared by means of double emulsion solvent evaporation method and optimized by applying 7-factor 2-level Plackett-Burman screening design. Results Spherical shaped NPs with homogeneous distribution, 188.95 nm particle size and 51.81% encapsulation efficiency were obtained. Liraglutide was successfully entrapped in the NPs while maintaining its native amorphous nature, and its structural integrity as well. Conclusion Lira-PLGA NPs with the required Critical Quality Attributes (CQAs) were successfully designed by implementing a 7-factor 8-run Plackett Burman design into the extended Quality by Design (QbD) model, to elucidate the effect of formulation and process variables on the particle size, size-distribution, encapsulation efficiency and surface charge. As the developed nanoparticles maintained the native structure of the active pharmaceutical ingredient (API), they are promising compositions for the further development for the oral delivery of Lira. Graphical
      PubDate: 2019-05-13
       
  • Characterization of Phosphate Buffered Saline (PBS) in Frozen State and
           after Freeze-Drying
    • Abstract: Purpose To study the effect of mannitol or trehalose on the crystallization behavior of solutes in phosphate buffered saline (PBS) when the solutions were frozen and freeze-dried. Methods PBS (pH 7.5 at RT) either alone, or with trehalose (5% w/v) or mannitol (1% w/v), were frozen and characterized using low temperature differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and pH measurement. Freeze dried lyophiles were characterized by XRD. Results In the absence of cosolutes, upon freezing PBS, a pH shift of ~ 4 units was observed due to crystallization of Na2HPO4•12H2O. XRD indicated sequential crystallization of Na2HPO4•12H2O, NaCl•2H2O and KCl during cooling. When the frozen solutions were heated, two eutectics were observed – the first at ~ −24°C (ternary, NaCl•2H2O-KCl-ice) and the second at ~ −22°C (binary, NaCl•2H2O-ice). Trehalose completely inhibited buffer salt crystallization, whereas mannitol suppressed it partially thereby attenuating the magnitude of pH shift. The two eutectic meltings were also suppressed by the cosolutes. XRD of final lyophiles from PBS alone revealed peaks of anhydrous Na2HPO4, NaCl, and KCl. Trehalose rendered the lyophiles completely XRD amorphous, whereas in presence of mannitol, all the solutes except KH2PO4 crystallized. Conclusions Freezing of PBS solution caused a pronounced pH shift due to selective crystallization of Na2HPO4•12H2O. The addition of trehalose or mannitol suppressed the buffer salt crystallization and attenuated the magnitude of pH shift. The potential instability of biologics due to pH shift in PBS, can be potentially mitigated with the cosolutes.
      PubDate: 2019-05-13
       
  • A Comprehensive Preclinical Evaluation of Intravenous Etoposide Lipid
           Emulsion
    • Abstract: Purpose Etoposide is one of the principal chemotherapeutic agents used for the treatment of small cell lung cancer (SCLC). There are some disadvantages of currently available etoposide injections (EI) such as low LD50, necessary dilution before clinical application, thus, etoposide lipid emulsion (ELE) was developed and expected to have a comparable or better effect on SCLC. Methods ELE was prepared through high-pressure homogenization method, and a series of evaluations such as encapsulation efficiency (EE%), in vitro release, stability studies, pharmacokinetics study, safety assessment and pharmacodynamic study were systematically performed. Results ELE had high EE% and good stability. Pharmacokinetics study revealed ELE had a longer T1/2 F compared with EI, which is in agreement with in vitro release in which ELE released slower than EI (EI released over 80% within 12 h, while ELE released 50%). Safety tests showed there was no hematology or significant tendency of accumulated toxicity, and LD50 of ELE was higher than EI. Furthermore, percentage of tumor inhibition (TI%) of ELE was comparable with EI in the same dose. Conclusions Unlike EI, ELE could further increase the dose, which endowed etoposide with a greater potential for cytotoxic agent. LE is a promising delivery system for etoposide.
      PubDate: 2019-05-10
       
  • Neutrophil-Mediated Delivery of Dexamethasone Palmitate-Loaded Liposomes
           
    • Abstract: Purpose The aim of this research was to design dexamethasone palmitate (DP) loaded sialic acid modified liposomes, with the eventual goal of using peripheral blood neutrophils (PBNs) that carried drug-loaded liposomes to improve the therapeutic capacity for rheumatoid arthritis (RA). Methods A sialic acid – cholesterol conjugate (SA-CH) was synthesized and anchored on the surface of liposomal dexamethasone palmitate (DP-SAL). The physicochemical characteristics and in vitro cytotoxicity of liposomes were evaluated. Flow cytometry and confocal laser scanning microscopy were utilized to investigate the accumulation of liposomes in PBNs. The adjuvant-induced arthritis was adopted to investigate the targeting ability and anti-inflammatory effect of DP loaded liposomes. Results Both DP-CL and DP-SAL existed an average size less than 200 nm with remarkably high encapsulation efficiencies more than 90%. In vitro and in vivo experiments manifested SA-modified liposomes provided a reinforced accumulation of DP in PBNs. As well, DP-SAL displayed a greater degree of accumulation in the joints and a stronger anti-inflammatory effect in terms of RA suppression. Conclusions SA-modified liposomal DP was a promising candidate for RA-targeting treatment through the neutrophil-mediated drug delivery system.
      PubDate: 2019-05-10
       
  • In Vivo -Relevant Transwell Dish-Based Dissolution Testing for Orally
           Inhaled Corticosteroid Products
    • Abstract: Purpose To establish an in vivo-relevant Transwell dish-based dissolution test system for the “respirable” aerosols of inhaled corticosteroids (ICSs) using marketed inhaler products. Methods “Respirable” ≤ 5.8 or 6.5 μm aerosols of 7 ICSs from 11 inhaler products were collected onto the filter membranes under the modified assembly of the cascade impactor. Their dissolution in 10 ml of the simulated lung lining fluid (sLLF) was determined over time in the Transwell dish at 37°C and ~100% relative humidity in the presence of subsequent diffusive permeation across the Transwell’s supporting membrane. Results While three ICSs with high-to-intermediate solubility enabled the first-order “sink” and complete dissolution in 6 h, 4 ICSs with poor solubility including fluticasone propionate (FP) resulted in the pseudo-zero-order “non-sink”, slow and limited dissolution. The aerosol dissolution rate constants (kdiss) were derived, well-correlated with the solubility. For FP, but not for highly-soluble flunisolide (FN), dissolution was kinetically aerosol mass-dependent. However, for a given ICS, dissolution profiles were indistinguishable between the formulations and products upon comparable aerosol mass collection. Conclusions The in vivo-relevant Transwell dish-based “respirable” aerosol dissolution test system was developed, kinetically discriminative in accordance with the ICS solubility, but indistinguishable for a given ICS between the marketed products.
      PubDate: 2019-05-09
       
  • On an Unphysical Hypothesis of Bateman Equation and its Implications for
           Pharmacokinetics
    • PubDate: 2019-05-08
       
  • Systemic Exposure of Rituximab Increased by Ibrutinib: Pharmacokinetic
           Results and Modeling Based on the HELIOS Trial
    • Abstract: Introduction In the HELIOS trial, bendamustine/rituximab (BR) plus ibrutinib (BR-I) improved disease outcomes versus BR plus placebo in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma. Here, we describe the pharmacokinetic (PK) observations, along with modeling to further explore the interaction between ibrutinib and rituximab. Methods 578 subjects were randomized to ibrutinib or placebo with BR (6 cycles). Ibrutinib PK samples and tumor measurements were obtained from all subjects; a subset was evaluated for bendamustine and rituximab PK. Population rituximab PK was assessed using nonlinear mixed-effects modeling. Results Dose-normalized plasma concentration-time bendamustine data were comparable between the arms. Systemic rituximab exposure was higher with BR-I versus BR; mean trough serum concentrations were 2- to 3-fold higher in the first three cycles and 1.2- to 1.7-fold higher subsequently. No relevant safety differences were observed. In the modeling, including treatment arm as a categorical covariate and tumor burden as a continuous time-varying covariate on overall rituximab clearance significantly improved fitting of the data. Conclusions BR-I led to higher dose-normalized systemic rituximab exposure versus BR and more rapid steady-state achievement. The modeling data suggest that rituximab disposition is, at least in part, target mediated. Determining the clinical significance of these findings requires further assessments. Trial Registration This study is registered at https://clinicaltrials.gov/ct2/show/NCT01611090.
      PubDate: 2019-05-01
       
  • Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray
           Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects
    • Abstract: Purpose Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. Methods Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 μg and 0.12 μg desmopressin subcutaneous (SC) bolus injection. Results AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 μg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5–6 h. Conclusions AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).
      PubDate: 2019-04-29
       
  • Dual Drugs Anticancer Nanoformulation using Graphene Oxide-PEG as
           Nanocarrier for Protocatechuic Acid and Chlorogenic Acid
    • Abstract: Background The chemotherapy of cancer has been complicated by poor bioavailability, adverse side effects, high dose requirement, drug resistance and low therapeutic indices. Cancer cells have different ways to inhibit the chemotherapeutic drugs, use of dual/multiple anticancer agents may be achieve better therapeutic effects in particular for drug resistant tumors. Designing a biocompatible delivery system, dual or multiple drugs could addressing these chemotherapy drawbacks and it is the focus of many current biomedical research. Methods In the present study, graphene oxide-polyethylene glycol (GOPEG) nanocarrier is designed and loaded with two anticancer drugs; Protocatechuic acid (PCA) and Chlorogenic acid (CA). The designed anticancer nanocomposite was further coated with folic acid to target the cancer cells, as their surface membranes are overexpressed with folate receptors. Results The particle size distribution of the designed nanocomposite was found to be narrow, 9-40 nm. The release profiles of the loaded drugs; PCA and CA was conducted in human body simulated PBS solutions of pH 7.4 (blood pH) and pH 4.8 (intracellular lysosomal pH). Anticancer properties were evaluated against cancerous cells i.e. liver cancer, HEPG2 and human colon cancer, HT-29 cells. The cytocompatbility was assessed on normal 3T3 fibroblasts cells. Conclusion The size of the final designed anticancer nanocomposite formulation, GOPEG-PCACA-FA was found to be distributed at 9-40 nm with a median of 8 nm. The in vitro release of the drugs PCA and CA was found to be of sustained manner which took more than 100 h for the release. Furthermore, the designed formulation was biocompatible with normal 3T3 cells and showed strong anticancer activity against liver and colon cancer cells.
      PubDate: 2019-04-24
       
  • Expedited Tablet Formulation Development of a Highly Soluble Carbamazepine
           Cocrystal Enabled by Precipitation Inhibition in Diffusion Layer
    • Abstract: Purpose To address the problem of precipitation of a poorly soluble drug during dissolution of highly soluble cocrystals by preparing granules intimately mixed with a water-soluble polymer. Methods Effectiveness of polymers as precipitation inhibitors during the dissolution of carbamazepine–nicotinamide (CBZ-NCT) cocrystal was assessed based on induction time of crystallization from a supersaturated solution in presence of different polymers at two concentrations. Dissolution was evaluated by both intrinsic dissolution rate (IDR) and USP dissolution method. Powder manufacturability was assessed using a shear cell and compaction simulator to assess flowability and tabletability, respectively. Results Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was the most effective polymer against precipitation of CBZ and the IDR of a 1:1 (w/w) CBZ-NCT/HPMCAS mixture was the highest. The final formulation of 1:1 CBZ-NCT/HPMCAS granule exhibited excellent flowability, good tabletability, and significantly improved drug release rate than cocrystal formulations without HPMCAS or the CBZ formulation. Conclusion The particle engineering strategy of modifying the diffusion layer on the surface of highly soluble cocrystal with a polymer is effective for inhibiting premature precipitation of CBZ. Assisted with predictive tools for characterizing powder flowability and tabletability, the design of high quality tablet product with improved drug release rate and manufacturability can be achieved in an efficient manner.
      PubDate: 2019-04-23
       
  • Correction to: Antimicrobial Drugs Encapsulated in Fibrin Nanoparticles
           for Treating Microbial Infested Wounds
    • Abstract: In the original manuscript, the Figure 2 a-i is inadvertently repeated as Figure 2 a-ii. This mistake has been rectified and the corrected Figure 2 is presented below.
      PubDate: 2019-04-19
       
 
 
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