Solid dispersions preparation methods

With the PGSS process, micronized drugs and drug/PEG 4000 samples were prepared in a new way, which has some advantages over conventional methods for the micronization of pure drugs and for drug/carrier solid dispersion preparation, namely fusion methods and solvent processes. 

Hasegawa, S.,Hamaura,T.,Furuyama,N.,Kusai,A.,Yonemochi, E.,andTerada,K. (2005), Effects of water content in physical mixture and heating temperature on crystallinity of troglitazone-PVP K30 solid dispersions prepared by closed melting method, Int. J. Pharm., 302,103-112. 

Hydroxypropyl Methylcellulose (HPMC) Suzuki and Sunada. report the production of solid dispersions prepared with nicotinamide and HPMC as combined carriers using nifedipine and nitrendipine as model drugs. Their solid dispersions were obtained using the fusion method. After both the drug and HPMC were dissolved in the liquid melt of nicotinamide at 140°C, the fused mixture was cooled to solidify it. 

McGinity, James W. Maincent philippe Steinfink, hugo. crystallinity and dissolution rate of tolbutamide solid dispersions prepared by the melt method. Pharm. Admin. 1984, 73 (10), 1441-1444. 

The activity and selectivity of a solid catalyst toward a desirable product are often limited by the randomness of the molecular arrangements of the active components in the catalysts prepared by traditional methods. It is therefore most challenging to devise new solid catalyst preparation methods to control metal dispersion, metal-support interaction, and pore structure on the molecular or nanometer level. It is equally challenging to form a heterogeneous catalyst without the need for further steps (catalytic or noncatalytic) to treat the effluents in the entire preparation process. Emerging new techniques in catalyst preparation are summarized in the following areas. 

Zajc, N., Obreza, A., Bele, M., and S. Srcic. Physical properties and dissolution behaviour of nifedipine/ mannitol solid dispersions prepared by hot melt method. Int J Pharm, 291 (2005) 51-58. 

Fig. 5.7 How chart of miniaturized screening to evaluate amorphous solid dispersion preparation and processing methods...

Woo JS, Kim HJ, Kim Y (2006) Method for the preparatin of paclitaxel sohd dispersion by using the supercritical fluid process and paclitaxel solid dispersion prepared thereby, Google Patents Yeo S-D, Kiran E (2005) Formation of polymer particles with supercritical fluids a review. J Supercrit Fluids 34(3) 287-308... 

Tachibana and Nakumara (100) introduced the concept of solid dispersion preparation by a solvent method. The proposed method involved dissolving the drug and water-soluble carrier in a common solvent and subsequent evaporation of the solvent under vacuum. Solid dispersions produced by this manner are commonly known as coprecipitates, a term coined by Bates (101). This term is a misnomer and should be appropriately renamed as coevaporates. In a strict sense, coprecipitates are formed by the addition of a second solvent to the original solution, which decreases the solubilities of the drug and carrier in the resultant solutions, thus coprecipitating them. 

The production of CLS by the melt dispersion technique is based on the melting of the lipid core material together with the lipophilic agent (i.e., phospholipids). Afterward, a warm aqueous solution is added to the molten material and is mixed by various methods (i.e., mechanical stirring, shaking, sonication, homogenization). Then the preparation is rapidly cooled until lipid solidification and the formation of particle dispersion. This method was used by Olbrich et al. [19] to produce the cationic solid lipid nanoparticles to use as novel transfection agent. 

Reaction-induced dispersion may be used as a substitute for conventional preparation methods for supported metal oxides (Wachs and Cai, 2001) it constitutes a particular case of solid—solid wetting, which is proposed to play an important role in catalyst preparation (Leyrer et al., 1990). Industrially relevant mixed metal oxide catalysts can be prepared by reaction-induced dispersion at temperatures that are significantly... 

Karasova G. Brandsteterova E. Lachova M. 2003. Matrix solid phase dispersion as an effective preparation method for food samples and plants before HPLC analysis. Czech J. Food Sci. 21 219-234. 

The principle of improving the solubility of poorly water-soluble drugs using solid dispersions has already been presented. One common method of preparing solid dispersions is melt-congealing. The carriers used to make solid dispersions of poorly water-soluble drugs have also been addressed. 

Suzuki and Sunada " also prepared solid dispersions of nifedipine with other combined carriers using a fusion (melt) method. The combined carriers were nicotinamide and four different water-soluble polymers hydroypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), partially hydrolyzed polyvinyl alcohol (PVA), and pullulan. HPMC, PVP, and PVA dissolved in the melt of nicotinamide and were effective in the amorphous formation of nifedipine in solid dispersions. In dissolution studies, the drug concentration... 

Chiou and Riegelman defined the term solid dispersion as a dispersion of one or more active ingredients in an inert carrier or matrix at solid state prepared by the melting (fusion), solvent, or melting-solvent method. Dispersions obtained through the fusion process are often called melts, and those obtained by the solvent method are frequently referred to as coprecipitates or coevaporates. Examples include sulfathia-zole-providone (PVP) and reserpine PVP. ... 

The two basic procedures used to prepare solid dispersions are the fusion and cosolvent techniques. Modifications of these methods and combinations of... 

Tachibana and Nakamura first used this method to prepare a solid dispersion of p-carotene in PVP by using chloroform as a cosolvent. The solvent is usually... 

Fassihi, Parker, and Pourkavoos used a combination of hydrophilic and lipophilic polymers to control the release rate. Thus, solid dispersions of theophylline were prepared by the fusion method using various ratios of PEG-6000, ethyl cellulose, and acrylic/ methacrylic esters. 

Controlled-release formulations of acetaminophen, aminopyrine, chlorpheniramine maleate, and salicylic acid that use Eudragit RSPM as a water-insoluble carrier, prepared by the solvent method, have been reported. A novel approach that uses a less soluble derivative of the drug as a carrier was used by Yang and Swarbrick to prepare sustained-release solid dispersions of dapsone. 

Solid dispersion particles made by spray-drying dis-ulfiram 1 1 or 1 2 (w/w) with PVP and instilled in the rabbit eye were found to have improved concentrations in the aqueous humor compared to 1 1 solid dispersions made by the evaporation method. In both cases, drug particles were passed through a 75 pm sieve. Particle size of the spray-dried particles had a D o of 3.3 0.04 pm, while those prepared by evaporation had a Dso of 34.3 18pm. ° ... 

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