Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids

Swellable and rigid matrices: controlled release matrices with cellulose ethers

none7Controlled release of drugs is a dynamic activity of pharmaceutical companies, due to the indisputable advancement provided by delivery technology to pharmacotherapy. In addition, this activity gives rise to new patented products for a market in which new substances are reducing and the approved ones more and more face administration problems. Today, no drug product enters the market without its own delivery program built in. In front of this requirement, pharmaceutical technology researchers proposed the so called drug delivery “technology platform,” i.e., drug administration based on the use of devices capable to contain, meter and deliver the drug at appropriate rate and duration. Typically, without considering drug conjugates, drug delivery devices are classified reservoirs or matrices. The choice between them depends on drug properties and delivery kinetics sought. In general, matrices are considered more reliable in term of delivery, less costly as manufacturing and easier to formulate. They are also less exposed to malfunctioning problems. Matrices are monolithic systems constituted of active substance dispersed and entrapped in a continuum of excipient (adjuvant), i.e., the “matrix forming” substance. The matrix requisite is the non-immediate disintegration of the monolith in contact with dissolution media. The usual appearance of this device is the tablet form, commonly manufactured by compression, that introduced in water does not apparently disintegrate. The maintenance of the solid structure permits the establishment of the mechanism for drug release control. Matrix keeps a substantial integrity or structure for the time needed to release the dispersed or dissolved drug. This does not mean that the matrix has not to dissolve but simply that dissolution is slowed down by its typical release mechanism. This behavior differentiates the disintegrating tablets from the matrices, the first promptly providing drug for dissolution and absorption, the second controlling in time drug dissolution and absorption. Here, drug release is obtained by elution from the polymeric (in general) continuum that can actively or passively participate to the release. Swellable matrices will be the subject of this chapter with the main focus on the swelling phenomenon and on the related drug release kinetics, in dependence on the components and matrix geometry used.noneP. COLOMBO; P. SANTI; J. SIEPMANN; G. COLOMBO; F. SONVICO; A. ROSSI; O.L. STRUSIP., Colombo; P., Santi; J., Siepmann; Colombo, Gaia; F., Sonvico; A., Rossi; O. L., Strus

Assembled modules technology for site-specific prolonged delivery of norfloxacin

The aim of this research was to design and study norfloxacin (NFX) release in floating conditions from compressed hydrophilic matrices of hydroxypropylmethylcellulose (HPMC) or poly(ethylene oxide) (PEO). Module assembling technology for drug delivery system manufacturing was used. Two differently cylindrical base curved matrix/modules, identified as female and male, were assembled in void configuration by friction interlocking their concave bases obtaining a floating release system. Drug release and floatation behavior of this assembly was investigated. Due to the higher surface area exposed to the release medium, faster release was observed for individual modules compared to their assembled configuration, independently on the polymer used and concentration. The release curves analyzed using the Korsmeyer exponential equation and Peppas & Sahlin binomial equation showed that the drug release was controlled both by drug diffusion and polymer relaxation or erosion mechanisms. However, convective transport was predominant with PEO and at low content of polymers. NFX release from PEO polymeric matrix was more erosion dependent than HPMC. The assembled systems were able to float in vitro for up to 240 min, indicating that this drug delivery system of norfloxacin could provide gastro-retentive site-specific release for increasing norfloxacin bioavailability. © 2010 Elsevier B.V. All rights reserved

Module assemblage technology for floating systems: In vitro flotation and in vivo gastro-retention

The aim of this research was to study, in vitro by resultant-weight measurement and in vivo by γ-scintigraphy experiments in humans, the floatation behavior of systems obtained by modules assembled in void configuration. The assembled system technology allowed the manufacturing of a system characterized by the presence of an internal void space that provided an apparent density lower than water. The gastro-retention times of floating assembled systems were determined in comparison with non-floating systems having the same mass and composition. In vitro the floatation of the system started immediately after immersion in water and lasted for more than 5 h. The in vivo studies confirmed that the in vitro floating ability of void configuration was maintained also in the human stomach where the system stayed for periods of time ranging from 2.5 to 5.0 h, depending on the food regimen and the sex of the subject. Reiterate eating and drinking further prolonged the stomach residence time. © 2008 Elsevier B.V. All rights reserved

Artesunate-clindamycin multi-kinetics and site-specific oral delivery system for antimalaric combination products

The aim of this work was to study a multi-kinetics and site-specific oral antimalaria drug delivery system (MKS_DDS), containing artesunate and clindamycin, based on the Dome Matrix® module assembly technology. The MKS_DDS assembled system comprises of four modules, i.e., two controlled release (CR) modules for delivery of 160. mg of clindamycin phosphate, one immediate release module containing 50. mg of artesunate and one immediate release module containing 80. mg of clindamycin phosphate. These modules have been assembled in stacked and void configurations. The void configuration is able to float and showed gastro-retentive behavior. The MKS_DDS was investigated for its mechanical characteristics, system behavior during release, drug release rate and mechanism.A bioavailability study (dogs) showed that the clindamycin plasma curve of the MKS_DDS system exhibited a quasi constant release rate, up to 8. h.The MKS_DDS system containing clindamycin and artesunate allows the use of one tablet containing one immediate release dose of artesunate and of clindamycin and a portion of clindamycin released over a prolonged time, by exploiting the gastro-retentive properties of a floating system. © 2010 Elsevier B.V