Samuel K. Owusu-Ware

Sirolimus Encapsulated Liposomes for Cancer Therapy: Physicochemical and Mechanical Characterization of Sirolimus Distribution within Liposome Bilayers

Sirolimus has recently been introduced as a therapeutic agent for breast and prostate cancer. In the current study, conventional and Stealth liposomes were used as carriers for the encapsulation of sirolimus. The physicochemical characteristics of the sirolimus liposome nanoparticles were investigated including the particle size, zeta potential, stability and membrane integrity. In addition atomic force microscopy was used to study the morphology, surface roughness and mechanical properties such as elastic modulus deformation and deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of deformation and lower packing density especially for dipalmitoyl-phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar results were obtained by differential scanning calorimetry (DSC) studies; sirolimus loaded liposomes were found to result in a distorted state of the bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform, greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC) Stealth liposomes.

Triboelectrification and dissolution property enhancements of solid dispersions

The use of solid dispersion techniques to modify physicochemical properties and improve solubility and dissolution rate may result in alteration to electrostatic properties of particles. Particle triboelectrification plays an important part in powder processing, affecting end product quality due to particle deposition and powder loss. This study investigates the use of glucosamine hydrochloride (GLU) in solid dispersions with indomethacin. Solvents selected for the preparation of the dispersions were acetone, acetone-water, ethanol and ethanol-water. Solid state characterizations (DSC, FTIR and XRPD) and dissolution were conducted. Dispersions were subjected to charge using a custom built device based on a shaking concept, consisting of a Faraday cup connected to an electrometer. All dispersions improved the dissolution rate of indomethacin. Analysis showed the method of preparation of the dispersion induced polymorphic forms of the drug. Indomethacin had a high propensity for charging (-411 nC/g). GLU had a very low charge (-1 nC/g). All dispersions had low charges (-1 to 14 nC/g). Acetone as a solvent, or in combination with water, produced samples with an electronegative charge in polarity. The same approach with ethanol produced electropositive charging. The results show the selection of solvents can influence powder charge thereby improving powder handling as well as dissolution properties.

Phase behaviour of dehydrated phosphatidylcholines

Dehydrated DLPC, DMPC, DPPC and DSPC have been characterised at temperatures below the diacyl carbon chain-melting transition (Tm), using DSC. For the first time, the existence of pre-Tm transition processes, which are, usually, only observed in the colloidal/liposomal state of saturated phospholipids, has been detected for the dehydrated phosphatidylcholines. Temperature-modulated differential scanning calorimetry was used to characterise the several complexes, overlapping pre-Tm transition processes. Kinetic studies of the chain-melting (Tm) transition show the activation energy dependence on α (conversion rate), i.e. activation energy decreases as the transition progresses, pointing to the importance of initial cooperative (intra- and inter-molecular) mobility. Furthermore, the activation energy increases with increase in diacyl chain length of the phosphatidylcholines which supports the finding that greater molecular interactions of the polymer chain and its head groups in the dehydrated solid state lead to enhanced stability of dehydrated phosphatidylcholines.

Molecular mobility of hydroxyethyl cellulose (HEC) films characterised by thermally stimulated currents (TSC) spectroscopy.

Molecular mobility has long been established to relate to textural properties and stability of polymer films and is therefore an important property to characterise to better understand pharmaceutical film formulations. The molecular mobility of solvent cast hydroxyethyl cellulose (HEC) films has been investigated by means of thermally stimulated current (TSC) below the temperature at which the film was formed. Preliminary physical characterisation of the films was performed using XRPD, TGA, DSC and texture analysis (tensile properties). XRPD results showed the films to be completely amorphous with Tg determined by DSC to be 127 ± 1°C. TGA analysis showed the films to contain 8 ± 1% water and film was dried to only 0.06 ± 0.01% water content when heated to 160°C. Application of TSC detected molecular mobility in HEC films at sub-zero temperatures. Two motional transitions with average relaxation time of 50 ± 3s were identified; a β-relaxation at -57 ± 2°C, attributed to localised non-cooperative orientation of HEC polymer chain ends and the hydroxyethyl side groups and an α-relaxation, originating from cooperative segmental mobility, at -20 ± 2°C. The tensile properties i.e., elongation, tensile strength and elastic modulus of the HEC film have been related to the molecular relaxation processes detected by TSC.

Thermal decomposition of chlorogenic acid in different atmospheres

Purpose: To model and interpret drug distribution in the dermis and underlying tissues after topical application which is relevant to the treatment of local conditions. Methods: We created a new physiological pharmacokinetic model to describe the effect of blood flow, blood protein binding and dermal binding on the rate and depth of penetration of topical drugs into the underlying skin. We used this model to interpret literature in vivo human biopsy data on dermal drug concentration at various depths in the dermis after topical application of 6 substances. This interpretation was facilitated by our in vitro human dermal penetration studies in which dermal diffusion coefficient and binding were estimated. Results: The model shows that dermal diffusion alone cannot explain the in vivo data and blood and/or lymphatic transport to deep tissues must be present for almost all of the drugs tested. Conclusion: Topical drug delivery systems for deeper tissue delivery should recognise that blood/ lymphatic transport may dominate over dermal diffusion for certain compounds.

Emollient product design: objective measurements of formulation structure, texture and performance, and subjective assessments of user acceptability

The choice of prescribed emollients is usually based on cost and patient preference. Differences in formulations can affect user acceptability.