Freeze drying—principles and practice for successful scale-up to manufacturing

Tsinontides, Stelios; Rajniak, Pavol; Pham, David; Hunke, W.A.; Placek, Jiří; Reynolds, Steven D.

doi:10.1016/j.ijpharm.2004.04.018

Cited by 105 publications

(49 citation statements)

References 7 publications

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“…However, there are some limitations of using these methods such as the degradation of drug due to the requirement of relatively high preparation temperatures, and the toxicity associated with the use of organic solvents. Freeze-drying is an industrial method which can keep the physical and chemical characters and biological activity of preparations and preserve the long-term stability (Tsinontides et al, 2004). Moreover, the drying process has clear influence on the surface of SD powders, which results in enhanced water uptake and wettability.…”

Section: Introductionmentioning

confidence: 99%

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Xie

Cao

et al. 2014

Drug Delivery

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This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and C max in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

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Section: Introductionmentioning

confidence: 99%

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Xie

Cao

et al. 2014

Drug Delivery

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“…The investigation of fundamental physical phenomena occurring during each step of freeze drying has enabled formulators to produce stable and well-designed freezedried pharmaceutical dosage forms [3]. Freeze dried products do not necessarily need to be refrigerated and can be stored at ambient temperatures.…”

Section: Introductionmentioning

confidence: 99%

Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs

Kianfar

Antonijević

Chowdhry

et al. 2013

Colloids and Surfaces B: Biointerfaces

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Lyophilized muco-adhesive wafers with optimum drug loading for potential buccal delivery have been developed. A freeze-annealing cycle was used to obtain optimized wafers from aqueous gels containing 2% κ-carrageenan (CAR 911), 4% pluronic acid (F127), 4.4% w/w polyethylene glycol with 1.8% w/w paracetamol or 0.8% w/w ibuprofen. Thermogravimetric analysis showed acceptable water content between 0.9 -1.5%. Differential scanning calorimetry and X-ray diffraction showed amorphous conversion for both drugs. Texture analysis showed ideal mechanical and mucoadhesion characteristics whilst both drugs remained stable over six months and drug dissolution at a salivary pH showed gradual release within two hours. The results show the potential of CAR 911 and F127 based wafers for buccal mucosa drug delivery.Keywords: Amorphous, Buccal drug delivery system, Carrageenan, Dissolution characteristics, Lyophilized wafer, (Muco)-adhesion, 3 IntroductionMucosal drug delivery systems have many advantages such as bypassing first pass liver metabolism and avoiding GI enzymatic degradation. Drug absorption via the buccal mucosa surface and into the systemic circulation is relatively fast (compared to the skin) owing to the highly vascularized structure underneath the mucosal tissues [1,2].Lyophilisation has been used in pharmaceutical industries to improve the stability of formulations. The investigation of fundamental physical phenomena occurring during each step of freeze drying has enabled formulators to produce stable and well-designed freezedried pharmaceutical dosage forms [3]. Freeze dried products do not necessarily need to be refrigerated and can be stored at ambient temperatures. This will be favourable for labile drugs including vaccines and proteins [4].Lyophilisation comprises a freezing step where ice crystals form and the solute becomes extremely concentrated. As the temperature falls below the glass transition temperature (T g ), the system is changed into a viscous glass. Incomplete crystallization may, however, lead to sample collapse or formation of mixtures of different polymorphic forms that causes problems in characterization and manufacturing reproducibility. Frozen products can be categorized as either crystalline or amorphous glass in structure. Crystalline products have a distinct "eutectic" freezing/melting point which is referred to as the collapse temperature. Amorphous products have a corresponding "glass transition" temperature and they are much more difficult to freeze-dry. Even though most materials that are freeze dried are actually amorphous, the term "eutectic" is often used to define the freezing/melting point of sample [4].To optimise the process of solute crystallization during freezing, thermal treatment, or "annealing", will be advantageous. Annealing is the process of heating a sample above its 4 glass transition temperature (but below the eutectic and/or ice melting temperature) and allowing the glass to relax and crystallize. Metastable glass formation is possible depending on the f...

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“…In addition, solid dispersions are prepared either by heating binder, drug and excipient to a temperature above the melting point of the binder (melt in procedure) or by spraying a dispersion of drug in molten binder on the heated excipient ( spray on procedure) by using a high shear mixer 71 .…”

Section: Melt Agglomeration Processmentioning

confidence: 99%

Untitled

2012

IJPSR

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Solubility is an important parameter to achieve desired concentration of drug in systemic circulation for pharmacological response to be shown. Among all newly discovered chemical entities most of the drugs are lipophillic and fail to reach market due to their poor water solubility. The solubility behavior remains one of the most challenging aspect informational development. Hence various techniques are used for the improvement of solubility of poorly water soluble drugs which include micronization, chemical modification, pH adjustment, solid dispersion, complexation, co-solvency micellar solubilization, hydrotrophy etc. Of all these approaches solid dispersion have attracted tremendous interest as an efficient means of improving the dissolution rate and hence the bioavailability to arrange of hydrophobic drugs. This article reviews the various preparation techniques and types of solid dispersion based on molecular arrangement. Finally some of the practical aspects have also been considered for the preparation of dispersions.

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Freeze drying—principles and practice for successful scale-up to manufacturing

Cited by 105 publications

References 7 publications

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers

Lyophilized wafers comprising carrageenan and pluronic acid for buccal drug delivery using model soluble and insoluble drugs

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