SEARCH · PubMed Health

Results for “Freeze Drying”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed2005

Physical characterisation of formulations for the development of two stable freeze-dried proteins during both dried and liquid storage.

The development of stable freeze-dried proteins requires maintaining the physical and biological integrity of the protein as well as increasing the efficiency of the manufacturing process. Our objective was to study the effects of various excipients on both the physical characterisation and the dried and liquid stability of two proteins. Thermo-physical properties of 13 formulations were determined using both differential scanning calorimetry and freeze-drying microscopy. The antigenic activity was evaluated immediately after freeze-drying and after subsequent storage in both dried and liquid state. From the comparison between glass transition (T'g) and collapse (T coll) temperatures, we concluded that the collapse temperature was a more relevant parameter than T'g for freeze-drying cycle development and optimisation. One crystalline formulation composed of 4% mannitol and 1% of sucrose protected efficiently both proteins during subsequent storage in dried state (6 months at 25 degrees C) and in liquid state (3 months at 4 degrees C after rehydration). However, the freeze-drying behaviour of this crystalline formulation remained difficult to predict and control. On the other hand, two amorphous formulations composed of 4% of maltodextrin and 0.02% of Tween 80, or 5% of BSA preserved antigenic activity during storage in dried state. The glassy character of these formulations as well as their high collapse temperature values (-9 and -12 degrees C, respectively) should allow simplification and shortening of freeze-drying process.

Calorimetry, Differential Scanning↗

PubMed2003

The effect of additives on the crystallization of cefazolin sodium during freeze-drying.

PURPOSE: To monitor the phase transitions during freeze-drying of cefazolin sodium (I) as a function of process and formulation variables. METHODS: Aqueous solutions of I were frozen under controlled conditions in the sample chamber of a variable temperature X-ray powder diffractometer (XRD). The instrument was modified so that the chamber could be evacuated and the samples dried under reduced pressures. Thus, the entire freeze-drying process was carried out in the XRD holder with real time monitoring of the phase transitions during the different stages of freeze-drying. RESULTS: When aqueous solutions of cefazolin sodium (10% w/w) were cooled to -40 degrees C, the XRD pattern revealed only the crystallization of ice. Annealing the frozen sample led to the crystallization of I as the pentahydrate. Differential scanning calorimetry revealed that the presence of isopropyl alcohol (IPA) (5% w/w) led to a decrease in the Tg', the glass transition temperature of the system, and lowered the temperature of crystallization. The crystallization was studied at -8 and at -15 degrees C in the XRD, and, as expected, more rapid crystallization was observed at the higher temperature. Primary drying at -8 degrees C led to the dehydration of the pentahydrate, resulting in a poorly crystalline product. Again, XRD permitted real time monitoring of the decrease in intensities of some characteristic peaks of the pentahydrate. The in situ XRD technique also enabled us to study the effects of processing conditions (different primary and secondary drying temperatures) and crystalline bulking agents on the solid-state of I in the lyophile. When I was lyophilized using mannitol or glycine as an additive, without an annealing step, the drug was X-ray amorphous although the additive crystallized. When annealed and freeze-dried, I remained crystalline in the presence of glycine but not in the presence of mannitol. CONCLUSIONS: The in situ XRD technique has enabled us to characterize the phase transitions during freeze-drying of cefazolin sodium in multicomponent systems.

Cefazolin↗

PubMed1971

Preservation of enteroviruses by freeze-drying.

A method was developed for freeze-dry stabilization of poliovirus type 3. An ultrafiltration procedure was used to remove salts from infected tissue culture fluid, and the virus was freeze-dried after suspension in an alkaline organic buffer. This method was further tested with other picornaviruses including poliovirus types 1 and 2, coxsackieviruses A9, A20, B2, and B5, echovirus 11, and the encephalomyocarditis virus. Freeze-dried preparations of the poliovirus could be shipped to distant laboratories at ambient temperature with excellent retention of infectivity. Data are presented showing effects of freeze-drying as well as results of exposure to temperatures to 37 C.

Buffers↗

PubMed2001

Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries.

In the present study, we examined the ability of dietary freeze-dried strawberries to inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. Initially, we conducted a bioassay to determine the effects of dietary freeze-dried strawberries on esophageal tumor development. Two weeks prior to NMBA treatment, animals were placed on a control diet or diets containing 5 and 10% freeze-dried strawberries. NMBA treatment was once per week for 15 weeks. At 30 weeks, 5 and 10% freeze-dried strawberries in the diet caused significant reductions in esophageal tumor multiplicity of 24 and 56%, respectively. Based on these results, we conducted studies to determine potential mechanisms by which freeze-dried strawberries inhibit tumorigenesis. In a short-term bioassay, we evaluated the effects of dietary freeze-dried strawberries on the formation of O6-methylguanine in the rat esophagus. Animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries for two weeks. At the end of this period, animals received a single subcutaneous dose of NMBA and were killed 24 h later. A significant decrease in O6-methylguanine levels was observed in the esophageal DNA of animals fed strawberries, suggesting that one or more components in strawberries influence the metabolism of NMBA to DNA-damaging species. Finally, in order to evaluate post-initiation effects, we conducted a study where freeze-dried strawberries were administered in the diet only following NMBA treatment. Animals were placed on control diet and dosed with NMBA three times per week for 5 weeks. Immediately following NMBA treatment, animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries. At 25 weeks, 5 and 10% freeze-dried strawberries in the diet significantly reduced tumor multiplicity by 38 and 31%, respectively. Our data suggest that dietary freeze-dried strawberries effectively inhibit NMBA-induced tumorigenesis in the rat esophagus.

Animals↗

PubMed2004

Reference materials for analytical toxicology including doping control: freeze-dried urine samples.

The feasibility of freeze-dried urine samples containing doping agents to be used in intercomparison exercises and/or as reference materials has been evaluated. Freeze-dried urine samples containing caffeine, ephedrine derivatives (ephedrine, methylephedrine, norephedrine, pseudoephedrine and norpseudoephedrine), amphetamine derivatives (amphetamine, metamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine) and testosterone and epitestosterone glucuronides have been evaluated. For preparation of the samples, blank urines previously subjected to filtration for clarification were fortified with standard solutions of the corresponding compounds and filtered under sterile conditions. Some aliquots of the sterile liquid samples were used for homogeneity testing, others were stored at -80 degree C for reference purposes, and the rest were subjected to lyophilisation. Freeze-dried urine samples were stored at 4-8 degree C and their stability was assessed for a period up to 18 months. Results obtained showed minimal differences (lower than 5%) between lyophilised and non-lyophilised aliquots (stored at -80 degree C) at all time periods except for amphetamine (up to 18%) and norpseudoephedrine (up to 10%). Nevertheless, such differences remained constant over the entire period of study, indicating that the loss of analytes was due to the initial lyophilisation process. The loss of analytes in freeze-dried samples was due to their volatility. Furthermore, an increase in pH by 1 unit was observed following reconstitution of samples prepared from drug-free urine of commercial origin.

Amphetamine↗

PubMed1983

Freeze dried cryoprecipitate: a clinical evaluation.

Freeze dried cryoprecipitate was used in the treatment of 14 patients with haemophilia A. The in vivo recovery was 91.2% which is comparable to that reported from other parts of Europe. The product was efficacious and no adverse effects were reported. Freeze dried cryoprecipitate is the high yield product of a low technology process and as such may be of value in reducing any possible shortfall in the factor VIII requirements of the haemophiliac population of the UK.

Chemical Precipitation↗

PubMed2003

Enhanced aqueous dissolution of a poorly water soluble drug by novel particle engineering technology: spray-freezing into liquid with atmospheric freeze-drying.

PURPOSE: The purpose of this work was to investigate spray-freezing into liquid (SFL) and atmospheric freeze-drying (ATMFD) as industrial processes for producing micronized SFL powders with enhanced aqueous dissolution. Micronized SFL powders dried by ATMFD were compared with vacuum freeze-dried SFL powders. METHOD: Danazol was formulated with polyvinyl alcohol (MW 22,000), polyvinylpyrrolidone K-15, and poloxamer 407 to produce micronized SFL powders that were freeze-dried under vacuum or dried by ATMFD. The powders were characterized using Karl-Fischer titration, gas chromatography, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, surface area, and dissolution testing (SLS 0.75%/Tris 1.21% buffer media). RESULTS: Micronized SFL powders containing amorphous drug were successfully dried using the ATMFD process. Micronized SFL powders contained less than 5% w/w and 50 ppm of residual water and organic solvent, respectively, which were similar to those contents detected in a co-ground physical mixture of similar composition. Micronized SFL powders dried by ATMFD had lower surface areas than powders produced by vacuum freeze-drying (5.7 vs. 8.9 m2/g) but significantly greater surface areas than the micronized bulk drug (0.5 m2/g) and co-ground physical mixture (1.9 m2/g). Rapid wetting and dissolution occurred when the SFL powders were introduced into the dissolution media. By 5 min, 100% dissolution of danazol from the ATMFD-micronized SFL powder had occurred, which was similar to the dissolution profile of the vacuum freeze-dried SFL powder. CONCLUSIONS: Vacuum freeze-drying is not a preferred technique in the pharmaceutical industry because of scalability and high-cost concerns. The ATMFD process enables commercialization of the SFL particle-engineering technology as a micronization method to enhance dissolution of hydrophobic drugs.

Calorimetry, Differential Scanning↗

PubMed2005

The effect of freeze-drying and its implications for botanical medicine: a review.

Botanical samples are often freeze-dried (lyophilized) for use in research studies, and a variety of freeze-dried botanicals are marketed to the public. In both instances, there is an underlying assumption that freeze-drying properly preserves the medicinal qualities of plants, and is superior to other preservation methods. In fact, little systematic research has been done to verify this assumption. A review of the existing research, done primarily by the food and spice industry, indicates that freeze-drying has unanticipated and significant effects on the constituent profiles of medicinal plants that puts into question whether freeze-drying necessarily is the best method to preserve botanical medicines.This research review finds there is insufficient information to conclude that freeze-drying has negative effects on the medicinal qualities of plants. But, because existing research indicates that freeze-drying imperfectly preserves important classes of medicinal compounds (such as volatiles, phenolics and carotenoids), may increase the mutation rate in unicellular organisms and may diminish some medicinal plant actions, researchers and practitioners should carefully consider how the use of freeze-dried material may affect pharmacological and clinical study results.

Carotenoids↗

PubMed2004

Activation, pronuclear formation, and development in vitro of pig oocytes following intracytoplasmic injection of freeze-dried spermatozoa.

The fertilization of pig oocytes following intracytoplasmic injection of freeze-dried spermatozoa was evaluated. Activation and male pronuclear (MPN) formation were better in oocytes injected with isolated freeze-dried sperm heads than whole freeze-dried spermatozoa, but cleaved embryos were generally difficult to develop to the morula or blastocyst stage. When spermatozoa were freeze-dried for 24 h, oocyte activation and MPN formation in activated oocytes after sperm head injection were inhibited. Embryo development to the blastocyst stage was only obtained after injecting sperm heads isolated from spermatozoa freeze-dried for 4 h and stored at 4 degrees C. The proportion of embryos that developed to the blastocyst stage was not increased by the treatment of injected oocytes with Ca ionophore (5-10 microM). Increasing the sperm storage time did not affect oocyte activation or MPN formation, but blastocyst development was observed only after 1 mo of storage. These results demonstrate that pig oocytes can be fertilized with appropriately freeze-dried spermatozoa and that the fertilized oocytes can develop to the blastocyst stage.

Animals↗

PubMed2005

Influence of lipid nanocapsules composition on their aptness to freeze-drying.

PURPOSE: To link the aptness to freeze-drying and the stability under storage to the topology of lipid nanocapsules. METHODS: The aptness to freeze-drying and the stability under storage of lipid nanocapsules prepared from different compositions with a lecithin content in the 2-20% range were estimated from the preservation of the physical structure, preventing the leakage of the oily phase. The influence of the outer shell composition and of the physical characteristics (investigated by photon correlation spectroscopy and differential scanning calorimetry) on the physical stability was correlated to the topology of the nanoparticulate carrier. RESULTS: Confirming the assumption that lecithin confers hardness to the outer shell of lipid nanocapsules, this study shows that the aptness to freeze-drying and the stability under storage depend on the Solutol/lecithin (S/L) ratio in the formulation. The DSC study points out a complexation between lecithin and trehalose, the cryoprotectant, reinforcing the stabilising properties of lecithin. CONCLUSIONS: This paper is a contribution to methodological development of the formulation of lipid nanocapsules, with a special emphasis on the aptness to freeze-drying and the stability under storage.

Freeze Drying↗

PubMed1997

Freeze drying of cardiac valves in preparation for cellular repopulation.

When freeze-dried cardiac valves have been implanted they remained acellular. This study is the initial step in the development of a method designed to repopulate the substance of the freeze-dried valve with fibroblasts and the lumenal surface with endothelial cells. In this scheme, the freeze-drying process performs three functions; it provides a porous matrix, it kills the donor cells, and it preserves the collagen structure and hence the mechanical strength of the valve. This paper describes the production of appropriate porosity in freeze-dried porcine pulmonary valve leaflets. We found that Tg' for this material is -83 degrees C, which made it impracticable to freeze-dry exclusively from the glassy state. Uncontrolled freeze-drying produced a variable structure with most of the pores considerably smaller than the desired size and a dense layer, apparently devoid of perforations, on the surface. Compacted layers also occurred within the substance of the leaflets. These appearances suggested that extensive collapse had occurred during the drying process. Variation of the cooling rate, the primary drying temperature, and the warming rate during secondary drying enabled us to identify the following conditions that provided satisfactory internal porosity: cooling at 5 degrees C/min, vacuum drying for 6 h at -20 degrees C, and secondary drying for 10 h during rewarming at 0.06-0.08 degrees C/min. The internal cavities measured 100-350 microns2 by ca. 400 microns2, which is adequate to provide access for the fibroblasts (cross-sectional area ca. 150-200 microns2 when rounded but fusiform when attached. However, the internal porous structure rarely communicated with the surface and mechanical perforation was required to provide continuity between the surface and the internal sponge. The resulting method provides a basis for studies of cell colonization.

Animals↗

PubMed2006

Fibres as carriers for Lactobacillus rhamnosus during freeze-drying and storage in apple juice and chocolate-coated breakfast cereals.

The capability of different fibre preparations to protect the viability and stability of Lactobacillus rhamnosus during freeze-drying, storage in freeze-dried form and after formulation into apple juice and chocolate-coated breakfast cereals was studied. In freeze-drying trials wheat dextrin and polydextrose proved to be promising carriers for the L. rhamnosus strains: both freeze-drying survival and storage stability at 37 degrees C were comparable to the control carrier (sucrose). Using apple fibre and inulin carriers resulted in powders with fairly good initial freeze-drying survival but with poor storage stability at 37 degrees C. When fresh L. rhamnosus cells were added into apple juice (pH 3.5) together with oat flour with 20% beta-glucan the survival of the cells was much better at 4 degrees C and at 20 degrees C than with sucrose, wheat dextrin and polydextrose, whereas with freeze-dried cells no protective effect of oat flour could be seen. The stability of freeze-dried L. rhamnosus cells at 20 degrees C was higher in chocolate-coated breakfast cereals compared to low pH apple juice. Similar to freeze-drying stability, wheat dextrin and polydextrose proved to be better carriers than oat flour in chocolate-coated breakfast cereals. Regardless of their differing capability to adhere to fibre preparations the two L. rhamnosus strains studied gave parallel results in the stability studies with different carriers.

Beverages↗

PubMed2005

Effect of protective agents, freezing temperature, rehydration media on viability of malolactic bacteria subjected to freeze-drying.

AIMS: The effects of protective agents, rehydration media and freezing temperature on the viabilities of Lactobacillus brevis and Oenococcus oeni H-2 when subjected to freeze-drying were investigated. METHODS AND RESULTS: Several protectants and rehydration media were tested to improve the survival after freeze-drying. The cells were also frozen at -65 and -20 degrees C to check the effect of freezing temperature on the viability. CONCLUSIONS: The best protectant and rehydration medium to obtain the highest viability after freeze-drying varied with the species of bacteria. Yeast extract (4.0%) and sodium glutamate (2.5% ) gave maximum viability of L. brevis and O. oeni (67.8% and 53.6% respectively). The highest survival of L. brevis and O. oeni were obtained when rehydrated with 10% sucrose and MGY medium respectively. When the bacterial cells were frozen quickly (-65 degrees C) than slowly (-20 degrees C), L. brevis and O. oeni both showed increased viability after freeze-drying. SIGNIFICANCE AND IMPACT OF THE STUDY: The viabilities of L. brevis and O. oeni after freeze-drying were shown to be strain specific and dependent on protective agents, rehydration media and freezing temperature.

Amino Acids↗

PubMed2005

Bioactive compounds of grapefruit (Citrus paradisi Cv. Rio Red) respond differently to postharvest irradiation, storage, and freeze drying.

In the present study, the effect of irradiation, storage, and freeze drying on grapefruit bioactive compounds was investigated. Grapefruits were exposed to one of two irradiation doses: 0 (control) or 300 Gy (137Cs, a proposed treatment against fruit flies) and then stored for up to 6 days. At the last storage time point (6 days after harvest), grapefruit pulp from control and irradiated fruits was freeze-dried. Bioactive compounds were extracted from Rio Red grapefruit pulp and analyzed with reverse phase liquid chromatography while volatile compounds were analyzed using gas chromatography. Freeze-dried pulp from irradiated fruits had a higher (P < or = 0.05) flavonoid content (naringin and narirutin) as compared to the freeze-dried pulp from the control fruits. Freeze-drying treatment reduced (P < or = 0.05) the lycopene content, but the reduction (P < or = 0.05) in beta-carotene content occurred only in the control fruit. Reduction in d-limonene and myrcene was observed in the irradiated fruits at 6 days after harvest and in the freeze-dried samples. These results warrant testing of the effect of postharvest treatments and processing on bioactive compounds in functional systems as they have varied effects on different bioactive compounds of grapefruit.

Ascorbic Acid↗

PubMed1987

Quantitative tissue isolation from Drosophila freeze-dried in acetone.

Freeze-drying procedures were developed to enable collection of tissues from Drosophila flies. The flies were frozen in acetone at -86 or -94 degrees C, and dehydrated therein. After drying, many tissues could be easily taken in entirety and free of neighbouring tissues without action of degradative enzymes. Seven polypeptide species specific to retina, and nine specific to cornea, were identified on two-dimensional electrophoretograms. Phospholipids of the dried tissues could be studied by t.l.c., and phosphatidic acid of the fly head was found to occur predominantly in the retina. Activity of three enzymes in the dried tissues could be assayed. The results of protein, phospholipid and enzyme analyses were corroborated by analyses by 'genetic dissection' using an eyeless mutant line.

Acetone↗

PubMed1991

Healing assessment of osseous defects of periapical lesions associated with failed endodontically treated teeth with use of freeze-dried bone allograft.

Freeze-dried bone allograft (FDBA) has been used extensively in periodontal surgery and in the treatment of pocket osseous defects resulting from inflammatory periodontal disease. No other endodontic investigation has used this type of graft material in the treatment of bony resorptive defects of the periapical lesions associated with failed endodontic therapy. Therefore this study was conducted with the use of FDBA, to assess healing ability of osseous defects after removal of periapical lesions associated with failed endodontically treated teeth. In all patients periapical lesions were surgically removed with retrograde amalgam seal and the graft material was then carefully packed without pressure into the bony defect. The lesions were fixed in 10% neutral buffered formalin and prepared for histologic examination. Long-term recall demonstrated bone regeneration and good tolerance of allograft material by the periapical tissues. The periapical lesions were either periapical granulomas or apical periodontal cysts. We conclude that FDBA is a biocompatible material of osteogenic potential and can be used effectively in treating osseous defects of periapical lesions associated with failed endodontically treated teeth.

Adolescent↗

PubMed1984

Studies on the antigenicity of bone. II. Donor-specific anti-HLA antibodies in human recipients of freeze-dried allografts.

UNLABELLED: Freeze-dried bone allografts from donors of known tissue type evoked donor-specific anti-HLA antibodies in nine of forty-three patients (forty-four procedures). Eight of the nine sensitized patients were followed roentgenographically for an average of twenty-three months and were known to have had a satisfactory resolution of the benign process for which the graft was employed. The ninth patient was doing well when lost to follow-up four months after receiving a bone allograft. CLINICAL RELEVANCE: The questions of whether immune responses to bone allografts occur in humans and, if so, adversely influence the incorporation of the graft can be answered at this time only by demonstrating the presence and frequency of such responses and how they correlate with clinical events. A large variety of techniques can be used to demonstrate immune responses. The technique that we used revealed that a small group of patients became sensitized to HLA antigens that were known to be present in the allograft donor but none of the recipients had evidence of adverse effects caused by the graft, as judged non-invasively.

Adolescent↗

PubMed1994

Effect of moisture content on the invertase activity of freeze-dried S. cerevisiae.

The invertase activity of intact Saccharomyces cerevisiae submitted to freezing-thawing was affected by pH, the chemical nature of the buffer, and the freezing cooling rate (CR), leading in some cases to a complete invertase inactivation (acetate buffer, pH 4.0, CR = 0.5 degree C/min). Once established under adequate freezing conditions the invertase activity remained unchanged after freeze-drying. Nevertheless, in some cases the cell-growing capability after freeze-drying diminished around 70%, mainly if the frozen cell suspension was attained through freezing carried out at CR = 0.5 degree C/min. Water sorption isotherms of freeze-dried samples (freeze-dryer Edwards L-4KR; 30 degrees C and 0.1 mB) were determined at 10 and 25 degrees C. The monolayer moisture content (MMC) at each temperature (12.7 and 3.71 for 10 and 25 degrees C, respectively) was calculated from isotherms by applying BET and GAB models. Freeze-dried yeast with water activity (Aw) between 0 and 0.33 (about the MMC value) maintained at 25 degrees C for 235 days and at 89 degrees C for 15 min retained at least 85% of its original invertase activity (IA), whereas samples with Aw > MMC lost at least 60% of its IA. X ray diffraction showed that the freeze-dried cake before and after storage presented an amorphous structure.

Buffers↗