Formulation and characterization of formaldehyde cross-linked degradable starch microspheres containing terbutaline sulfate.

Preparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18-24 microm. Whatever the cross-linking time, it was seen that the release of the TBS was not complete during the release experiments. The influence of enzyme on the degradation of microspheres was moderate. Following intravenous administration, initial uptake of microspheres by the lung was higher than those of other organs.

Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.

Drug delivery to brain by microparticulate systems.

The site specific delivery of chemotherapeutic agents allows maximum concentration of an agent at a desired body site. This area specific drug delivery decreases the unwanted systemic distribution and decreases toxicity of the administered drugs. Blood-Brain Barrier (BBB) is considered to be an obstacle in delivering large number of drugs to brain. The endothelial cells forming the tubular capillaries in the brain are cemented together by intercellular tight junctions. In this way, the BBB has an important role in providing a stable extracellular environment in the central nervous system. Lack of fenestrations, very few pinocytotic vesicles, and more mitochondria are other differences of the brain capillaries which play important role in transport of drugs to brain (Fig.1). The purpose of this paper is to summarise the methods for BBB permeability modifications and to focus on various examples in delivering drugs, especially neuroncology and neuroactive drugs, to brain by microparticulate systems.

Preparation, characterization and in vivo distribution of terbutaline sulfate loaded albumin microspheres.

Terbutaline sulfate is widely used as a bronchodilator for the treatment of bronchial asthma, chronic bronchitis and emphysema. As it has a short biological half-life, a long acting terbutaline sulfate formulation is desirable to improve patient compliance. Bovine serum albumin microspheres were prepared by an emulsion polymerization method using glutaraldehyde as the crosslinking agent. All microspheres were spherical and smooth with the mean particle size in the range of 22-30 microm. Drug release from the BSA microspheres displayed a biphasic pattern characterized by an initial fast release, followed by a slower release. The released amount was decreased with an increase in the glutaraldehyde concentration. In the absence of trypsin, the time required for complete degradation of microspheres was increased from 144 to 264 h when the glutaraldehyde concentration increased from 0.1 to 0.7 ml. In the presence of trypsin, a linear relationship was obtained between the degradation rates and trypsin concentrations, indicating that saturation was not reached under the experimental conditions. Biodistribution studies indicated that the degree of uptake by the lungs was higher than that of the other organs. All these results demonstrated that terbutaline sulfate loaded microspheres can be used for passive lung targeting.

Influence of irradiation sterilization on poly(lactide-co-glycolide) microspheres containing anti-inflammatory drugs.

Gamma-irradiation is finding increasing use in the sterilization of pharmaceutical products. However, irradiation might also affect the performance of drug delivery systems. In this study, the influence of gamma-irradiation on the physicochemical properties of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) [naproxen sodium (NS) and diclofenac sodium (DS)] was investigated. The drugs were incorporated in poly(lactide-co-glycolide) (PLGA, 50:50; molecular weight 34000 or 88000 Da) microspheres. The biodegradable microspheres were irradiated at doses of 5, 15, 25 kGy using a 60Co source. Drug loading of irradiated and non-irradiated microspheres with both 34000 and 88000 Da polymers were essentially the same. A significant difference was noticed in the particle sizes of the irradiated as compared to the non-irradiated formulations. Notably, in release studies, the amount of active substance released from PLGA microspheres showed an increase with increasing irradiation dose. In DSC, the glass transition temperatures (Tg) of microspheres exhibited a slow increase with irradiation dose.