ABSTRACT
Lipid implants prepared by melting and casting offer a great potential for advanced drug delivery. However, care must be taken with respect to the solid state of the lipid(s) and potential changes thereof during storage. Generally, a thermal aftertreatment is required. However, little is known about the impact of the curing time and temperature on drug release. The aim of this study was to better understand the importance of these parameters for different types of implants containing propranolol hydrochloride. Hydrogenated cottonseed oil and hydrogenated soybean oil were used as matrix formers. The implants were characterized with respect to their in vitro release kinetics, water uptake, thermal properties, and morphology. On the basis of these experimental results, a mechanistic mathematical model was used to gain further insight into the underlying mass transport mechanisms. Both the curing time and the temperature strongly affected the resulting drug release patterns. Importantly, in most cases, these effects could not be attributed to polymorph transformations but to changes in the implants' microstructure. The size of the lipid particles depended on both the curing time and the temperature, and determined the size of the pores/channels through which water and drug diffuse. The importance of this aspect is often underestimated.
Subject(s)
Cottonseed Oil/chemistry , Drug Delivery Systems/methods , Drug Implants , Soybean Oil/chemistry , Technology, Pharmaceutical/methods , Calorimetry, Differential Scanning , Microscopy, Electron, Scanning , Models, Chemical , Particle Size , Phase Transition , Powders , Propranolol/administration & dosage , Propranolol/chemistry , Solubility , Surface Properties , Temperature , Time Factors , Water/chemistryABSTRACT
The parenteral controlled delivery of acid-labile drugs (e.g., proteins) is difficult, because the standard polymer poly(lactic-co-glycolic acid) used to control drug release upon parenteral administration degrades into shorter chain acids, creating acidic microclimates. Lipid implants do not show this disadvantage. The objective of this article is to give an overview on the present state of the art and to highlight the advantages and drawbacks of the different types of systems reported in the literature. The major preparation techniques for lipid implants, underlying mass transport mechanisms, biocompatibility and in vivo performance of the most interesting systems are described. Lipid implants offer a great potential as parenteral controlled drug delivery systems, especially for protein-based drugs. A broad spectra of release patterns can be provided and acidic microclimates avoided.