Maltodextrin-based proniosomes.

Niosomes are nonionic surfactant vesicles that have potential applications in the delivery of hydrophobic or amphiphilic drugs. Our lab developed proniosomes, a dry formulation using a sorbitol carrier coated with nonionic surfactant, which can be used to produce niosomes within minutes by the addition of hot water followed by agitation. The sorbitol carrier in the original proniosomes was soluble in the solvent used to deposit surfactant, so preparation was tedious and the dissolved sorbitol interfered with the encapsulation of one model drug. A novel method is reported here for rapid preparation of proniosomes with a wide range of surfactant loading. A slurry method has been developed to produce proniosomes using maltodextrin as the carrier. The time required to produce proniosomes by this simple method is independent of the ratio of surfactant solution to carrier material and appears to be scalable. The flexibility of the proniosome preparation method would allow for the optimization of drug encapsulation in the final formulation based on the type and amount of maltodextrin. This formulation of proniosomes is a practical and simple method of producing niosomes at the point of use for drug delivery.

SEM imaging predicts quality of niosomes from maltodextrin-based proniosomes.

PURPOSE: The limits to surfactant loading of proniosomes were determined and a rationale developed for the observed relationship between the composition of proniosomes and the quality of reconstituted niosome suspension. METHODS: A novel method for producing proniosomes with a maltodextrin carrier was recently developed, which provides for rapid reconstitution of niosomes with minimal residual carrier. A slurry of maltodextrin and surfactant was dried to form a free-flowing powder which could be rehydrated by addition of warm water. This method provided facile production of a wide range of proniosome compositions, and thus, allowed us to examine rehydration behavior for similar concentrations of surfactant over a wide range of film thickness. SEM images of proniosomes with various degrees of surfactant loading and images of pure surfactant were compared. Direct observation and particle size measurements by laser light scattering provided characterization of the final niosome preparations. RESULTS: Successful rehydration of surfactant to produce niosomes from dried film requires that the film be as thin as possible to avoid the clumping and precipitation that occurs when pure, granular surfactant is hydrated directly. The appearance of a coarse, broken surface on the proniosomes correlates with inefficient rehydration and occurrence of aggregation and precipitate in the final niosome suspension. CONCLUSIONS: These observations provide an indication of the requirements for dry proniosomes to yield niosome suspensions of high quality.

Quantitative NMR imaging study of the mechanism of drug release from swelling hydroxypropylmethylcellulose tablets.

NMR imaging has been used to study the release behavior of two model drugs, triflupromazine-HCl and 5-fluorouracil, from swelling hydroxypropylmethylcellulose (HPMC) tablets. Preliminary experiments were performed on equilibrium mixtures of drug, polymer and water to determine how properties such as NMR relaxation parameters and self-diffusion were affected by the drug and polymer concentrations. The tablet swelling was restricted to one dimension and distributions of the water and model drugs were obtained by 1H and 19F imaging, respectively. The HPMC distribution at each time in the swelling process was determined indirectly from its effect on the relaxation parameters of the water and the drugs. In the one-dimensional swelling tablet, distributions of drug and polymer were compared to determine what factors influenced the release of drug from the swelling tablet. The distributions for triflupromazine-HCl and HPMC paralleled each other and the drug was only released at the eroding edge of the tablet where the HPMC concentration dropped below 10%. In contrast, 5-fluorouracil was released much more rapidly from the tablet and appeared to escape by diffusion from regions as high as 30% HPMC. An empirical measure of the rate of tablet edge movement can be obtained from plots of the edge position as a function of the square root of time. For HPMC, the rate of tablet expansion was determined in this way to be (2.4+/-0.8)x10(-6) cm(2) s(-1). The self-diffusion of triflupromazine-HCl in equilibrated mixtures of similar composition to the eroding tablet edge is approximately 3x10(-6) cm(2) s(-1) while the self-diffusion coefficient of 5-fluorouracil remained higher than this value until the HPMC concentration reached about 30%. This comparison of 'diffusion' properties may be useful in predicting the mechanism of drug release from other swelling hydrophilic matrix systems.

NMR imaging investigations of drug delivery devices using a flow-through USP dissolution apparatus.

A system for performing NMR imaging experiments on drug delivery devices within a flow-through dissolution apparatus, USP Apparatus 4, has been developed. The system was used to image the physical changes that occur in solid dosage forms during dissolution in the flow-through apparatus. Simultaneous cumulative drug release measurements were also made. The NMR images obtained under these conditions and the drug release data provide a better understanding of the processes involved in the release of drugs from drug delivery systems based on diffusion, dissolution and osmosis mechanisms.