Combination Of Mannitol Research Articles

Příprava a hodnocení sprejově sušených inhalovatelných mikročástic ze směsí nosičů

The formulation of microparticles composed of a mixture of carriers represents an innovative approach for lung drug delivery of dry powder. The carriers used can significantly influence the properties of the microparticles, such as size, shape, surface area, hygroscopicity, or aggregation, thus improving the aerosolization of the drugs after inhalation. The properties mentioned above are crucial for effective pulmonary therapy. The combination of carriers of a carbohydrate nature and gelling agents is advantageous for controlled drug release. The experimental work aimed to prepare by spray drying and subsequently evaluate ten batches of microparticles composed of sugar-based carriers (mannitol, maltodextrin, dextran) and gelling polymers (chitosan, chondroitin sulfate) and to select a suitable combination for follow-up experimental work aimed at drug incorporation into the microparticle matrix. The most suitable parameters were exhibited by batches whose aerodynamic diameter was close to 5 µm, particles prepared from a combination of mannitol and dextran, chitosan and chondroitin, or maltodextrin and chondroitin. These batches also showed the highest fine particle fraction value (> 43%). From a processability point of view, the batch with maltodextrin and chondroitin is preferable due to the lower viscosity of the dispersion and the more regular shape of the final microparticles.

Drug Utilization Study of Diuretics in Children with Hydrocephalus

Hydrocephalus is a condition characterized by a dynamic imbalance between formation and absorption of cerebrospinal fluid that increases the size of intracranial space of the brain and, in some situations, an extension of the outer space of the brain with or without increased ventricular size. This study aimed to examine the use of diuretics and identify drug therapy problems in hospitalized children with hydrocephalus through the medical record. The study design is observational retrospective with time-limited sampling based on data in medical records at 2010-2013 periods, found 17 of 70 patients using diuretics therapy. There are three categories of diuretic which are used were mannitol (70.6%), acetazolamide (23.5%), and a combination of mannitol and acetazolamide (5.9%). Diuretics can be used for pre-op, post-op, and pre & post-op on all types of hydrocephalus. Still, the specific use of diuretics may be caused by variations in comorbid diagnoses, clinical data, and laboratory data for each patient. Adverse drug reactions are potentially dominant in DTP analysis, and these are 7 of 17 patients. Monitoring of serum electrolytes such as sodium and potassium is needed because it decreases are potential adverse drug reactions of diuretics.

Improved Pressure Equalization Ratio Following Mannitol Administration in Patients With Severe TBI: A Preliminary Study of a Potential Bedside Marker for Response to Therapy.

BackgroundPerforming a cerebrospinal fluid (CSF) drainage challenge can be used to measure the pressure equalization (PE) ratio, which describes the extent to which CSF drainage can equalize pressure to the height of the external ventricular drain and may serve as a correlate of cerebral edema. We sought to assess whether treatment with mannitol improves PE ratio in patients with severe traumatic brain injury (TBI) with elevated intracranial pressure (ICP).MethodsWe studied consecutive patients with TBI and brain edema on computed tomography scan and an external ventricular drain (EVD), admitted to the neurointensive care unit. PE ratio, defined as ICP prior to CSF drainage minus ICP after CSF drainage divided by ICP prior to CSF drainage minus EVD height, was measured as previously described. Patients were treated with mannitol for raised ICP based on clinical indication and PE ratio measured before and after mannitol administration.ResultsWe studied 20 patients with severe TBI with raised ICP. Mean ICP prior to mannitol treatment was 29 ± 7 mm Hg. PE ratio rose substantially after mannitol treatment (0.62 ± 0.24 vs. 0.29 ± 0.20, p < 0.0001), indicating an improved ability to drain CSF and equalize ICP with the preset height of the EVD. The combination of mannitol and CSF drainage led to an improved reduction in ICP compared with that seen before mannitol therapy (11 ± 2 mm Hg vs. 6 ± 2 mm Hg, p < 0.01), and led to a decrease in ICP below the 20 mm Hg threshold in 77% of cases.ConclusionsTreatment with mannitol leads to a substantial improvement in PE ratio that reflects the ability to achieve a greater decrease in ICP when CSF drainage is performed after mannitol administration. This preliminary study raises the possibility that PE ratio may be useful to follow response to therapy in patients with cerebral edema and raised ICP. Further studies to determine whether PE ratio may serve as an easily obtained and clinically useful surrogate marker for the extent of brain edema are warranted.

O6-4 The effect of intravenous mannitol in combination with normal saline on the prevention of cisplatin-induced nephrotoxicity: A randomized, double-blind, placebo-controlled trial

O6-4 The effect of intravenous mannitol in combination with normal saline on the prevention of cisplatin-induced nephrotoxicity: A randomized, double-blind, placebo-controlled trial

Disintegrant Properties of Microcrystalline Cellulose isolated from Rami (Boehmeria nivea L. Gaud) in Dimenhydrinate tablets by Wet Granulation and Direct compression

Microcrystalline cellulose was isolated from rami (Boehmeria Nivea L. Gaud), and applied as disintegrant in tablets of dimenhydrinate, made by direct compression and wet granulation. The aim of this study is to produce dimenhydrinate tablets with Microcrystalline Cellulose Rami (MCC Rami) isolated from Rami (Boehmeria Nivea L. Gaud), as a disintegrant and assess the effect of MCC Rami and Granulation technique on physical properties of drug such as, disintegration time, drug release and dissolution. Formulations of dimenhydrinate 100mg tablets were prepared with a combination of mannitol and lactose as a filler and MCC Rami as disintegrant in a concentration of 10-20%. The formulas were directly compressed or were compressed into tablets after wet granulation. The mechanical properties, drug release, physical properties and effects of process parameters, methods of applying disintegrant in tablet formulas were examined. A significant difference in disintegration time of tablets that were produced by direct compression and wet granulation was seen, that can be attributed to the porous structure of granules that enhanced fast disintegration, which had eventually improved dissolution and drug release. F1 and F2 with MCC Rami and physical mixture of MCC Rami with crosspovidone as a disintegrant that were directly compressed disintegrated in 79 and 72 seconds respectively thats not a significant difference, however when MCC was applied in an intragranular way its disintegration time is 67 seconds. The results showed that the method of disintegrant application and press of tableting has a significant effect on drug release and dissolution.Keywords : Microcrystalline Cellulose, wet granulation, disintegrant, Boehmeria Nivea L. Gaud.

Formulating a Stable Mannitol Infusion while Maintaining Hyperosmolarity.

Mannitol infusion is commonly used in the treatment of intracranial hypertension following traumatic brain injury. It has long been known to have stability issues, specifically, mannitol recrystallises from solutions greater than 10% w/v in ambient conditions. This can happen at any time, whether on the pharmacy shelf or during a medical procedure. This study describes the stability limits of 20% w/v mannitol infusion (the most common strength used clinically) and proposes a number of safer, stable and tuneable hyperosmotic formulations of mannitol in combination with clinically acceptable osmotic agents (NaCl, sorbitol and glycerol).

Hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury.

Hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury.

Evaluation of Efficacy of Hypertonic Saline and Mannitol in Combination in Patients with a Traumatic Brain Injury

Evaluation of Efficacy of Hypertonic Saline and Mannitol in Combination in Patients with a Traumatic Brain Injury

Mannitol and the Combination of Mannitol and Gelatin Impair Whole Blood Coagulation and the Platelet Function In Vitro

Mannitol 20% and succinylated gelatin 4% are routinely used in neurosurgical procedures. The aim of this in vitro study was to explore the influence of both agents on blood coagulation and platelet function. Blood from 21 healthy volunteers was obtained and then diluted so as to form five groups: (1) 7% dilution with mannitol; (2) 10% dilution with gelatin; (3) 17% dilution with isotonic balanced electrolyte solution; (4) 17% dilution with mannitol+gelatin; and (5) undiluted blood. The extrinsic thrombelastometry (EXTEM) and fibrin thrombelastometry (FIBTEM) tests were examined by rotational thrombelastometry via ROTEM®, and thrombocyte aggregometry with the aspirin inhibiting- (ASPI), adenosine diphosphate- (ADP), and thrombin-activating protein (TRAP) tests performed by Multiplate. In the EXTEM test clot formation time, the alpha angle, and maximum clot firmness were significantly reduced by mannitol and the combination of mannitol with gelatin. The platelet function tested in the ADP test was also significantly reduced with this combination. In this in vitro study, clinically relevant dilutions of mannitol and gelatin showed a significant inhibition of whole blood coagulation and the platelet function, which could be detrimental in neurosurgical settings.

Application of Texture Analysis Technique in Formulation Development of Lyophilized Orally Disintegrating Tablets Containing Mannitol, Polyvinylpyrrolidone and Amino Acids.

Orally disintegrating tablets (ODTs) attract a great attention as this easy swallowing dosage form often improves patient compliance. In the current work, orally disintegrating tablets comprising mannitol, polyvinylpyrrolidone (PVP) and an amino acid (alanine, glycine or serine) with various PVP-to-amino acid ratios were formulated. The combination of mannitol and an amino acid was aimed to use the advantages of mannitol, the matrix-supporting and disintegration agent, and to reduce the total amount of sugar/polyol in tablets. Tablets were manufactured by freeze-drying and their properties (appearance, internal structure, disintegration, mechanical and texture properties, moisture uptake, shrinkage, thermal properties) were assessed. In the work, great emphasis was placed on illustrating the applicability of the Texture Analysis of the freeze-dried cakes directly in vials in formulation development. The results show that the appearance, mechanical properties, disintegration and shrinkage of the freeze-dried ODTs depend significantly on the excipient composition with PVP playing the leading role. Partial mannitol replacement with an amino acid has a limited impact on the tablet properties. The presence of an amino acid also has no impact on the PVP-mannitol interaction. The mechanical and texture properties of freeze-dried ODTs depend non-linearly on the PVP content. The transition between the different types of textures occurs in a narrow range of PVP concentrations regardless of the type of amino acid in a formulation. The non-linear effect of PVP on various tablet properties should be taken into account when designing ODT formulations as it can compromise the robustness of the manufacturing process.

The combination of mannitol and temozolomide increases the effectiveness of stem cell treatment in a chronic stroke model

BackgroundThe blood-brain barrier (BBB) presents a significant challenge to the therapeutic efficacy of stem cells in chronic stroke. Various methods have been developed to increase BBB permeability, but these are associated with adverse effects and are, therefore, not clinically applicable. We recently identified that combination drug treatment of mannitol and temozolomide improved BBB permeability in vitro. Here, we investigated whether this combination could increase the effectiveness of stem cell treatment in an animal model of chronic ischemic stroke. MethodsChronic stroke was induced in rats by middle cerebral artery occlusion (MCAo). After then, rats were administered human umbilical cord–derived mesenchymal stromal cells (hUC-MSCs) by intravenous injection with or without combination drug treatment of mannitol and temozolomide. To evaluate the therapeutic efficacy, behavioral and immunohistochemical tests were performed, and the differences among control, stem cell only, combination drug only and stem cell with combination drug treatment were analyzed. ResultsAlthough no hUC-MSCs were detected in any group, treatment with stem cells and combination drug of mannitol and temozolomide increased the intracerebral delivery of hCD63-positive microvesicles compared with stem cell only treatment. Furthermore, treatment with stem cells and drug combination ameliorated behavioral deficits and increased bromodeoxyuridine-, doublecortin- and Reca-1–positive cells in the perilesional area as compared with other groups. DiscussionThe combination drug treatment of mannitol and temozolomide allowed for the efficient delivery of hUC-MSC–derived microvesicles into the brain in a chronic stroke rat model. This attenuated behavioral deficits, likely by improving neural regeneration and angiogenesis. Thus, combination drug treatment of mannitol and temozolomide could be a novel therapeutic option for patients with chronic ischemic stroke.

Phytase overexpression in Arabidopsis improves plant growth under osmotic stress and in combination with phosphate deficiency

Engineering osmotolerant plants is a challenge for modern agriculture. An interaction between osmotic stress response and phosphate homeostasis has been reported in plants, but the identity of molecules involved in this interaction remains unknown. In this study we assessed the role of phytic acid (PA) in response to osmotic stress and/or phosphate deficiency in Arabidopsis thaliana. For this purpose, we used Arabidopsis lines (L7 and L9) expressing a bacterial beta-propeller phytase PHY-US417, and a mutant in inositol polyphosphate kinase 1 gene (ipk1-1), which were characterized by low PA content, 40% (L7 and L9) and 83% (ipk1-1) of the wild-type (WT) plants level. We show that the PHY-overexpressor lines have higher osmotolerance and lower sensitivity to abscisic acid than ipk1-1 and WT. Furthermore, PHY-overexpressors showed an increase by more than 50% in foliar ascorbic acid levels and antioxidant enzyme activities compared to ipk1-1 and WT plants. Finally, PHY-overexpressors are more tolerant to combined mannitol stresses and phosphate deficiency than WT plants. Overall, our results demonstrate that the modulation of PA improves plant growth under osmotic stress, likely via stimulation of enzymatic and non-enzymatic antioxidant systems, and that beside its regulatory role in phosphate homeostasis, PA may be also involved in fine tuning osmotic stress response in plants.

Impact of Drug Formulation Variables on Silicone Oil Structure and Functionality of Prefilled Syringe System.

Use of prefilled syringes to self-administer biologics via subcutaneous administration provides convenience to patients. The barrel interior of prefilled syringes is typically coated with silicone oil for lubrication to aid plunger movement at the time of administration. This study intended to evaluate the impact of formulation variables on the silicone oil on the barrel interior surface. Characterization techniques including syringe glide force, break loose force, Schlieren imaging, contact angle, inductively coupled plasma spectrometry, and thin film interference reflectometry were used in assessing the interactions. Data indicated that formulation variables such as pH, buffer/tonicity agent type and concentration, and surfactant present in the formulation can effect silicone oil lubrication of prefilled syringes, leading to changes in functional properties of the syringe over time. Syringe samples containing acetate and histidine buffers showed an increase in glide force at accelerated storage temperature conditions, but the change was minimal at 5 °C. The samples with the highest glide force correlated with the presence of mannitol in combination with sodium acetate buffer. Sodium chloride had lesser impact on glide force than mannitol. Samples with higher glide force exhibited a substantial change in the silicone oil layer of the syringe, as observed with Schlieren imaging, as well as a significant reduction in surface hydrophobicity, as demonstrated through contact angle measurement. These data indicated that the structure of the siliconized surface can change over time in contact with different formulations. During formulation development of drug products in prefilled syringes, in addition to potential impact on molecule stability, the selection of formulation variables should also be guided by assessing the impact to syringe functionality with the glide force as one of the key parameters.LAY ABSTRACT: Self-administering drug products packaged in prefilled syringes provides convenience to patients. The interior of a prefilled glass syringe is typically lubricated with silicone oil for easy plunger movement during injection. This article discusses the impact of formulation excipients on silicone oil coating inside the syringe. Characterization techniques were used to assess the ease of plunger movement and structure of the silicone coating. Data indicate formulation excipients can affect silicone oil distribution of prefilled syringes, leading to an increase in plunger glide force at accelerated storage temperature conditions. The increase in glide force within a prefilled syringe with or without an auto-injector can have an impact on dose accuracy and user experience. Syringes with a higher plunger glide force appeared to exhibit a change over time in surface energy and structure of the silicone oil layer in contact with particular formulations.

Free radical scavenging properties of mannitol and its role as a constituent of hyaluronic acid fillers: a literature review.

Mannitol has both hydrating and antioxidant properties that make it an ideal excipient for use with hyaluronic acid (HA) fillers. This review examines the role of reactive oxygen species in the ageing process and their effects on both endogenous HA and HA products developed for aesthetic use. Evidence is presented to show that the free radical scavenging properties of mannitol provide it with a two-fold mechanism of action when combined with HA fillers: reducing the inflammation and swelling associated with the injection procedure itself, and preventing the degradation of the injected HA by free radicals. Mannitol also has a long- and well-established safety profile in both the food and pharmaceutical industry. Having established the rationale for using mannitol in combination with an HA filler, the products using this strategy are then reviewed. The addition of mannitol to HA fillers is a viable and safe option for improving both short- and long-term HA aesthetic effects.

Efficient Stable in Vitro Micropropagation and Conservation of Tinospora cordifolia (Willd.)Miers: an Anti-diabetic Indigenous Medicinal Plant

An efficient protocol is described for the rapid in vitro multiplication of Tinospora cordifolia (Willd.) Miers., an important indigenous medicinal plant, via enhanced shoot bud proliferation from shoot tip explants. This plant has great importance to different pharmaceutical industry for its medicinal value and mainly harvested from the wild population is resulting an over-exploitation of natural habits. To avoid this alarming situation and to ensure its continuous supply, plant tissue culture technique was applied. The explants cultured on to MS medium containing different concentrations of BAP, Kn and NAA either alone or in combination for investigation of morphogenetic response. The best shoot proliferation (16.5±0.25) was observed MS media supplemented with 5.0 mg l−1 BAP alone. The highest shoot elongation observed MS medium containing 1.0 mg l−1 BAP in combination with 0.6 mg l−1 GA3 (12.5±1.5 cm). The maximum rooting frequency (82.00±3.0%) obtained from the MS medium in the combination 1.0 mg l−1 IBA. For in vitro conservation, the best response (95%) was achieved using 2% sorbitol and 2% mannitol in combination with MS medium at 10°C temperature up to 8 months by in vitro slow growth technique. Regenerated plantlets were transferred to greenhouse conditions and observed 90.00±0.4% survival frequencies. The diploid status (2n=24) of regenerated plantlets as well as mother plant was determined using chromosome counts of root-tips. Berberine content (0.218%) in regenerated plants was determined by using HPTLC and HPLC methods. It is concluded that the regenerated plants were stable in respect to their morphology, chromosome number and berberine content, which offers a unique opportunity to obtain true-to-type plants as source plant.

OPTIMIZATION OF LOZENGES FORMULA OF SENGGUGU ROOT BARK (Clerodendrum serratum L. Moon) EXTRACTS FOR MUCUS DILUENT (MUCOLITIC) IN COMBINATION WITH MANNITOL-LACTOSE-SUCROSE FILLERS

Senggugu root bark (Clerodendrum serratum L. Moon) is known as a mucolitics. Senggugu root bark is made in the dosage form of lozenges in combination with sucrose, mannitol and lactose in order to obtain good flavor and comfortable when consumed. The purpose of this study was to determine the effect of the combination of fillers on the physical properties of granules and tablets as well as the composition of the combination of excipients to produce lozenges of extract of senggugu root bark with optimum physical properties. Seven formulas were made with a combination of mannitol, lactose and sucrose as follows: FI (100%: 0%: 0%), FII (0%: 100%: 0%), FIII (0%: 0%: 100%), FIV (50 %: 50%: 0%), FV (50%: 0%: 50%), FVI (0%: 50%: 50%), and FVII (33.3%: 33.3%: 33.3% ). The results showed that the combination of mannitol, lactose and sucrose affected the physical properties of the granules and lozenges of extract of senggugu root bark i.e. flow rate, hardness, dissolved time, compactibility and perceptive sense. The dominant amount of sucrose and lactose can improve the physical properties of granules and tablets. The optimal composition of the combination of mannitol, lactose and sucrose obtained from Design Expert 7.1.5. program was 5.491%: 37.387%: 57.122%, respectively.

Method for Isolating Mitochondrial DNA from Etiolated Tissue of Cabbage

Isolation of high-quality mitochondrial DNA (mtDNA) is an important premise for researching molecular mechanisms in cytoplasmic male sterility of cabbage (Brassica oleracea L.var.capitata). An efficient protocol for separation and purification of mitochondria and extraction of mitochondrial DNA (mtDNA) from etiolated tissues of cabbage was developed. We took a method combined mannitol density gradient with differential centrifugation, selected appropriate rotational speed, extended DNase I treating time and changed mitochondria cracking condition. The results showed that the extracted mitochondria in this protocol had complete structure, appeared to ellipsoid and had not been contaminated with other impurities under the Jannus Green B staining. The isolated mitochondrial DNA had high purity and yield through detecting the optical density, nuclear specific primer PCR and agarose gel electrophoresis. The results indicated that mitochondrial DNA extracted by this protocol had high quality and enabled to be used in futher genetic studies.

Coagulation effects of mannitol in combination with 0.9% normal saline or hydroxyethyl starch in patients undergoing supratentorial craniotomy: A preliminary report

Abstract Background: Neurosurgical patients often require administration of both, mannitol and hydroxyethyl starch (HES). A recent in vitro study demonstrated that HES in combination with mannitol could disturb coagulation parameters and should be avoided in neurosurgical practice. The aim of our study was to evaluate coagulation abnormalities due to mannitol when administered alone and in combination with HES in patients undergoing craniotomy for various intracranial brain tumours. Materials and Methods: We enrolled 30 adult patients undergoing craniotomy. Patients were randomised into two groups using a computer generated randomisation chart. Interventions: Group A: Patients received 10 ml/kg 0.9% normal saline and 1 g/kg mannitol and Group B: Patients received 10 ml/kg, HES 130/0.4, and 1 gm/kg mannitol; immediately after induction of general anaesthesia. Rotational thromboelastography was done immediately after induction of general anaesthesia and 5 min after administration of mannitol. Measured parameters of blood coagulation were clotting time (CT) and clot formation time (CFT) with EXTEM and maximum clot firmness (MCF) with EXTEM and (FIBTEM). Results: Fourteen patients in each group completed the study. Insignificant change was noted in CT; CFT altered significantly from the baseline in both the groups (P &lt; 0.05). MCF with FIBTEM did not change significantly from baseline (P &gt; 0.05), but significantly differed between groups (P = 0.001). However, all values were in normal range. Conclusion: Mannitol 1 g/kg and HES 10 ml/kg can be safely administered in patients undergoing craniotomy for supratentorial tumours, without clinically significant changes in coagulation parameters.

A74 Coagulation Effects of Combination of Mannitol and 0.9% Normal Saline or Hydroxy-ethyl-starch in Neurosurgical Patients

A74 Coagulation Effects of Combination of Mannitol and 0.9% Normal Saline or Hydroxy-ethyl-starch in Neurosurgical Patients

Suitability of differently formulated dry powder Newcastle disease vaccines for mass vaccination of poultry

Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6°C and 25°C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6–2.0 log10 50% egg infectious dose (EID50) and storage at 6°C (max. 0.8 log10 EID50 after 6months) in combination with a low moisture content (1.1–1.4%), low hygroscopicity (1.9–2.1% water uptake at 60% relative humidity) and good dry dispersibility properties.