ABSTRACT
CONTEXT: Many active substances are poorly water-soluble and pose a great challenge when orally administered because drug bioavailability is largely dependent on its solubility. OBJECTIVE: The objective of this investigation was to evaluate the effect of hydroxypropyl methylcellulose (HPMC) as an additive on the physical properties of spray-congealed polyethylene glycol (PEG) microparticles. MATERIALS AND METHODS: The effects of four viscosity grades of HPMC (K100 LV, K4M, K15M and K100M) on the spray-congealing process yield and physical properties of spray-congealed microparticles, such as morphology and particle size, were studied. The swelling effect of HPMC on drug release was also explored using surface plots. RESULTS AND DISCUSSION: Molten mixtures containing PEG and HPMC of various grades and concentrations were successfully spray-congealed with useful yield ranging from 42.6% to 58.4%. Smooth and spherical microparticles were produced and their size was found to increase with increasing feed viscosity. The swelling extent of microparticles was found to be influenced by the grade, particle size and amount of HPMC present while the rate of erosion depended on the formation of the barrier and grade of HPMC used. Formulations with appropriate rates of erosion were selected to prepare microparticles with rifampicin (RIF), a poorly water-soluble drug. At 10% (w/w), K100 LV was found to enhance the dissolution of RIF while K15M retarded the release. CONCLUSION: The novel application of HPMC as an additive in spray-congealed PEG microparticles not only affected the physical properties of the microparticles but also modified the drug release by its swelling effect.
Subject(s)
Chemistry, Pharmaceutical/methods , Hypromellose Derivatives/chemistry , Microspheres , Polyethylene Glycols/chemistry , Rifampin/chemistry , Drug Liberation , Hypromellose Derivatives/pharmacokinetics , Particle Size , Polyethylene Glycols/pharmacokinetics , Rifampin/pharmacokinetics , Solubility , ViscosityABSTRACT
The purpose of this study was to investigate the effect of a hydrophilic polymer, hydroxypropyl methylcellulose (HPMC), on the crystallinity and drug release of metronidazole (MNZ) in spray-congealed polyethylene glycol (PEG) microparticles and to further modify the drug release using other additives in the formulation. HPMC has been used in many pharmaceutical formulations and processes but to date, it has not been employed as an additive in spray congealing. Crystallinity of a drug is especially important to the development of pharmaceutical products as active pharmaceutical ingredients (APIs) are mostly crystalline in nature. A combination of X-ray diffractometry, differential scanning calorimetry, Raman spectroscopy and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy was employed to investigate the degree of crystallinity and possible solid-state structure of MNZ in the microparticles. The microparticles with HPMC were generally spherical. Spray congealing decreased MNZ crystallinity, and the presence of HPMC reduced the drug crystallinity further. The reduction in MNZ crystallinity was dependent on the concentration of HPMC. Smaller HPMC particles also resulted in a greater percentage reduction in MNZ crystallinity. Appreciable modification to MNZ release could be obtained with HPMC. However, this was largely attributed to the role of HPMC in forming a diffusion barrier. Further modification of drug release from spray-congealed PEG-HPMC microparticles was achieved with the addition of 5% w/w dicalcium phosphate but not with magnesium stearate, methyl cellulose, polyvinylpyrrolidone, silicon dioxide and sodium oleate/citric acid. Dicalcium phosphate facilitated formation of the diffusion barrier.
Subject(s)
Hypromellose Derivatives/chemistry , Metronidazole/chemistry , Polyethylene Glycols/chemistry , Calorimetry, Differential Scanning/methods , Chemistry, Pharmaceutical/methods , Crystallization/methods , Drug Liberation , Microspheres , Particle Size , Povidone/chemistry , Solubility , Spectroscopy, Fourier Transform Infrared/methods , Spectrum Analysis, Raman/methods , X-Ray Diffraction/methodsABSTRACT
An understanding of the rheological behaviour of polymer melt suspensions is crucial in pharmaceutical manufacturing, especially when processed by spray congealing or melt extruding. However, a detailed comparison of the viscosities at each and every temperature and concentration between the various grades of adjuvants in the formulation will be tedious and time-consuming. Therefore, the statistical method, principal component analysis (PCA), was explored in this study. The composite formulations comprising polyethylene glycol (PEG) 3350 and hydroxypropyl methylcellulose (HPMC) of ten different grades (K100 LV, K4M, K15M, K100M, E15 LV, E50 LV, E4M, F50 LV, F4M and Methocel VLV) at various concentrations were prepared and their viscosities at different temperatures determined. Surface plots showed that concentration of HPMC had a greater effect on the viscosity compared to temperature. Particle size and size distribution of HPMC played an important role in the viscosity of melt suspensions. Smaller particles led to a greater viscosity than larger particles. PCA was used to evaluate formulations of different viscosities. The complex viscosity profiles of the various formulations containing HPMC were successfully classified into three clusters of low, moderate and high viscosity. Formulations within each group showed similar viscosities despite differences in grade or concentration of HPMC. Formulations in the low viscosity cluster were found to be sprayable. PCA was able to differentiate the complex viscosity profiles of different formulations containing HPMC in an efficient and time-saving manner and provided an excellent visualisation of the data.
Subject(s)
Hypromellose Derivatives/chemistry , Polyethylene Glycols/chemistry , Suspensions/chemistry , Chemistry, Pharmaceutical/methods , Particle Size , Polymers/chemistry , Principal Component Analysis , Temperature , ViscosityABSTRACT
INTRODUCTION: In any manufacturing process, the success of producing an end product with the desired properties and yield depends on a range of factors that include the equipment, process and formulation variables. It is the interest of manufacturers and researchers to understand each manufacturing process better and ascertain the effects of various manufacturing-associated factors on the properties of the end product. Unless the manufacturing process is well understood, it would be difficult to set realistic limits for the process variables and raw material specifications to ensure consistently high-quality and reproducible end products. Over the years, spray congealing has been used to produce particulates by the food and pharmaceutical industries. The latter have used this technology to develop specialized drug delivery systems. AREAS COVERED: In this review, basic principles as well as advantages and disadvantages of the spray congealing process will be covered. Recent developments in spray congealing equipment, process variables and formulation variables such as the matrix material, encapsulated material and additives will also be discussed. EXPERT OPINION: Innovative equipment designs and formulations for spray congealing have emerged. Judicious choice of atomizers, polymers and additives is the key to achieve the desired properties of the microparticles for drug delivery.
