7 research outputs found
Kinetic and thermodynamic evaluation of phosphate ions binding onto sevelamer hydrochloride
Sevelamer hydrochloride is the first non-aluminium, non-calcium-based phosphate binder developed for
the management of hyperphosphatemia in end stage renal diseases. It is a synthetic ion-exchange
polymer which binds and removes phosphate ions due to the high content of cationic charge associated
with protonated amine groups on the polymer matrix. This is the first in-depth study investigating
phosphate removal in vitro from aqueous solutions using commercially available sevelamer
hydrochloride at physiological conditions of phosphate level, pH and temperature. The kinetic and
thermodynamic parameters of phosphate binding onto the sevelamer hydrochloride particles were
evaluated in order to define the binding process. A series of kinetic studies were carried out in order to
delineate the effect of initial phosphate concentration, absorbent dose and temperature on the rate of
binding. The results were analysed using three kinetic models with the best-fit of the experimental data
obtained using a pseudo-second order model. Thermodynamic parameters provide in-depth information
on inherent energetic changes that are associated with binding. Free energy DG�, enthalpy DH�, and
entropy DS� changes were calculated in this study in order to assess the relationship of these parameters
to polymer morphology. The binding reaction was found to be a spontaneous endothermic process with
increasing entropy at the solid–liquid interface
Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System
The formulation of oral amorphous
solid dispersions (ASD) includes
the use of excipients to improve physical stability and enhance bioavailability.
Combinations of excipients (polymers and surfactants) are often employed
in pharmaceutical products to improve the delivery of poorly water-soluble
drugs. However, additive interactions in multicomponent ASD systems
have not been extensively studied and may promote crystallization
in an unpredictable manner, which in turn may affect the physical
stability and dissolution profile of the product. The main aim of
this study was to understand the effect of different surfactant and
polymer combinations on the solid-state properties and dissolution
behavior of ternary spray-dried solid dispersions of dipyridamole
and cinnarizine. The surfactants chosen for this study were sodium
dodecyl sulfate and poloxamer 188, and the model polymers used were
polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The
spray-dried ternary dispersions maintained higher supersaturation
compared to either the crystalline drug equilibrium solubility or
their respective physical mixtures. However, rapid and variable dissolution
behavior was observed for different formulations. The maximum supersaturation
level was observed with drug–polymer–polymer ternary
dispersions. On the other hand, incorporating the surfactant into
binary (drug–polymer) and ternary (drug–polymer–polymer)
ASDs adversely affected the physical stability and dissolution by
promoting crystallization. On the basis of these observations, a thorough
investigation into the impact of combinations of additives on amorphous
drug crystallization during dissolution and stability studies is recommended
in order to develop optimized formulations of supersaturating dosage
forms
Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease
Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED
Investigation into the Stability, Crystallization Kinetics, and Heating Rate Dependent Crystallization of Amorphous Posaconazole
Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan
Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated. Mucoadhesive formulations can decrease precorneal clearance while prolonging precorneal residence. Thus, they are expected to enhance the chances of adherence to corneal and conjunctival surfaces and as such, enable increased delivery to the posterior eye segment. Among the mucoadhesive polymers available, chitosan is the most widely explored due to its outstanding mucoadhesive characteristics. In this review, the major PSEDs, their treatments, barriers to topical delivery, and routes of topical drug absorption to the posterior eye are presented. To enable the successful design of mucoadhesive ophthalmic drug delivery systems (DDSs), an overview of mucoadhesion, its theory, characterization, and considerations for ocular mucoadhesion is given. Furthermore, chitosan-based DDs that have been explored to promote topical drug delivery to the posterior eye segment are reviewed. Finally, challenges of successful preclinical to clinical translation of these DDSs for posterior eye drug delivery are discussed