A Drug Delivery System (DDS) may provide the precise transportation of the medical drug inside the patient’s body, directly to the pathological area or alternatively it may be locally administrated. Some unique features of chitosan (CH) including its biocompatibility and biodegradability together with the ability of hydroxyapatite (HAP) to adsorb and then release different chemical species make these compounds attractive materials for a DDS design.
The present work addresses the combination of hydroxyapatite nanoparticles (nHAP), and CH with a drug model aimed at engineering a controlled DDS. Dexamethasone (DEX) is the drug model here selected.
Composite granules with different ratios of HAP and CH were produced by spray drying aqueous suspensions of HAP, CH and DEX. To control polymer swelling, Glutaraldehyde (GA) was used to cross-link CH. Granules were also produced by a double spray drying technique, which has not been yet addressed in the literature. Double spray dried granules were prepared in 2 stages: firstly a suspension of HAP was stirred with DEX until complete drug dissolution and then spray dried. Secondly, the collected granules were then added to a solution of CH in acetic acid and the final suspension spray dried.
The obtained results showed that the variation of (HAP/CH) ratio affected the morphology of the granules. When this ratio increases the granules morphology changes from spherical with rough surface to a shape with concavities and smooth surface. Regarding the granules obtained by double spray drying, their morphological characteristics suggested that a core-shell structure was obtained.
      The drug release experiments were carried out by immersing the DEX loaded granules into phosphate buffer solution (PBS), at 37 °C under constant stirring. Aliquots of PBS were withdrawn after different times and their drug content evaluated. The results showed that cross-linked granules exhibit a more sustained release than GA free granules with the same HAP/CH ratio. Double spray dried granules showed a release profile with a double plateau: after an initial fast release, which is a feature common to the other release patterns, a first plateau appears followed then by a second steep release that tends to a new plateau. These results suggest that the initial fast release of the superficial drug leads to a plateau as no more drug is available to be released. However, prolonging the release time allows the erosion of CH surface layer which gives access to the drug encapsulated in inner regions enabling then a second fast release which evolves later to a second plateau. This behavior is in line with a core-shell structure.
Attempting to clarify the mechanisms that underly DEX release in order to identify the experimental variables that enable the optimization of the DDS, different mathematical models were compared with the measured release profiles. The obtained results showed that Peppas-Sahlin and Weibull equations are appropriate models for predicting the drug release from the produced granules which can be categorized as diffusion-controlled systems.
In conclusion, the cross-linking and morphology engineering (core-shell structure) via double spray drying allowed improving DEX release profile of HAP/CH DDSs.