Unlocking the full potential of lipid-based formulations using lipophilic salt/ionic liquid forms.

Lipid-based formulations (LBF) are widely used by industry and accepted by the regulatory authorities for oral drug delivery in the pharmaceutical and consumer healthcare market. Innovation in the LBF field is however needed in order to meet the demands of modern drugs, their more challenging problem statements and growing needs for achieving optimal pharmacokinetics (i.e.

Transformation of Biopharmaceutical Classification System Class I and III Drugs Into Ionic Liquids and Lipophilic Salts for Enhanced Developability Using Lipid Formulations.

Higher lipid solubility of lipophilic salt forms creates new product development opportunities for high-dose liquid-filled capsules. The purpose of this study is to determine if lipophilic salts of Biopharmaceutical Classification System (BCS) Class I amlodipine and BCS Class III fexofenadine, ranitidine, and metformin were better lipid formulation candidates than existing commercial salts. Lipophilic salts were prepared from lipophilic anions and commercial HCl or besylate salt forms, as verified by H-NMR.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 5. Lipolysis of representative formulations by gastric lipase.

Purpose: Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 6: effects of varying pancreatin and calcium levels.

The impact of pancreatin and calcium addition on a wide array of lipid-based formulations (LBFs) during in vitro lipolysis, with regard to digestion rates and distribution of the model drug danazol, was investigated. Pancreatin primarily affected the extent of digestion, leaving drug distribution somewhat unaffected. Calcium only affected the extent of digestion slightly but had a major influence on drug distribution, with more drug precipitating at higher calcium levels.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 4: proposing a new lipid formulation performance classification system.

The Lipid Formulation Classification System Consortium looks to develop standardized in vitro tests and to generate much-needed performance criteria for lipid-based formulations (LBFs). This article highlights the value of performing a second, more stressful digestion test to identify LBFs near a performance threshold and to facilitate lead formulation selection in instances where several LBF prototypes perform adequately under standard digestion conditions (but where further discrimination is necessary). Stressed digestion tests can be designed based on an understanding of the factors that affect LBF performance, including the degree of supersaturation generated on dispersion/digestion.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 3: understanding supersaturation versus precipitation potential during the in vitro digestion of type I, II, IIIA, IIIB and IV lipid-based formulations.

Purpose: Recent studies have shown that digestion of lipid-based formulations (LBFs) can stimulate both supersaturation and precipitation. The current study has evaluated the drug, formulation and dose-dependence of the supersaturation - precipitation balance for a range of LBFs.

Methods: Type I, II, IIIA/B LBFs containing medium-chain (MC) or long-chain (LC) lipids, and lipid-free Type IV LBF incorporating different doses of fenofibrate or tolfenamic acid were digested in vitro in a simulated intestinal medium.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout.

Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations.

The Lipid Formulation Classification System Consortium is an industry-academia collaboration, established to develop standardized in vitro methods for the assessment of lipid-based formulations (LBFs). In this first publication, baseline conditions for the conduct of digestion tests are suggested and a series of eight model LBFs are described to probe test performance across different formulation types. Digestion experiments were performed in vitro using a pH-stat apparatus and danazol employed as a model poorly water-soluble drug.

C1-esterase inhibitor infusion increases survival rates for patients with sepsis*.

Objectives: Systemic inflammatory response variability displays differing degrees of organ damage and differing outcomes of sepsis. C1-esterase inhibitor, an endogenous acute-phase protein, regulates various inflammatory and anti-inflammatory pathways, including the kallikrein-kinin system and leukocyte activity. This study assesses the influence of high-dose C1-esterase inhibitor administration on systemic inflammatory response and survival in patients with sepsis.

[Safety and efficacy of purified human C1-esterase inhibitor in the treatment of patients with sepsis].

One of the new experimental trends in pharmacotherapy of sepsis is the use of C1-esterase inhibitor (C1I) from the group of immunobiological agents influencing the complement system. An open prospective study on the safety and efficacy of C1I revealed its positive effect on the death rate among the patients with sepsis. In a dose of 12000 IU, C1I had a significant inhibitory action on the complement system activity, as well as an antiinflammatory effect by blocking the complement-dependent link in the systemic inflammation.

[Forced medical care for convicts with drug addiction].

An analysis of the dynamics of unlawful activity of alcohol and drug addicts is carried out. All forms of treatment of drug addictions, either voluntary or forced, are considered as relevant to the prevention of repeated unlawful activity of convicts with drug addiction. Principles and basic criteria for the assignment of forced treatment of alcoholism and drug addiction to convicts are presented.

Circulating cytokines as markers of systemic inflammatory response in severe community-acquired pneumonia.

Objectives: To assess the influence of empirical antibacterial therapy on systemic inflammatory response in patients with severe community-acquired pneumonia (CAP).

Material And Methods: Thirty consecutive patients with CAP meeting systemic inflammatory response syndrome (SIRS) criteria were recruited into this study. Blood samples for measurement of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and C-reactive protein (CRP) concentrations were drawn on days 1, 3, 5, 7 and 10.

[Principles of antibacterial therapy of sepsis].

For the last decade understanding of sepsis pathogenesis has changed much. A significant role pathogenesis of sepsis is assigned to systemic inflammatory reaction provoking imbalance in different links of antiinfection protection. Antibiotics remain the only available group of drugs which can improve prognosis in sepsis.

The monoethylglycinexylidide (MEGX) test as a marker of hepatic dysfunction in septic patients with pneumonia.

The aim of this study was to monitor hepatic function in patients with pneumonia meeting the sepsis criteria of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) and to determine if hepatic dysfunction is related to the systemic inflammatory response. Twenty patients were recruited. The monoethylglycinexylidide (MEGX) test was carried out on days 1-10 after admittance to the intensive care unit.

[Interrelation between indices of the progression of alcoholism and various premorbid factors].

A clinical study of 720 alcoholic patients was performed. The material obtained was statistically processed by correlation analysis in order to investigate the relationship between the disease progression and some premorbid factors. Indices of alcoholism progression included qualitative assessment of progression, duration of regular alcohol consumption and the length of disease stages, as well as the patients' age at the time of alcoholism formation and at the initiation of treatment.

[Significance of several factors for actualization of the pathologic drive to alcohol in chronic alcoholism].

On the basis of literary data and clinical experience, a list of 27 factors was compiled, which could have a significance for actualizing pathological drives to alcohol in chronic alcoholism. The factors were marked under such headings as "individual", "family-environmental" and "connected with the environment at work". In order to establish the connection of each factor with the actualization of a pathological drive to alcohol, 200 inpatients treated for chronic alcoholism were examined.

[Experience with the use of lithium salts in the treatment of chronic alcoholism].

Lithium salts were given to 88 patients with chronic alcoholism and affective disorders in the clinical picture (32 of the patients received lithium for more than 3 months). Positive results were seen in those cases where pathology of the affective sphere was marked in the premorbid period of alcoholism and was only aggravated in the formation of alcoholism. The absence of any affect was found in those cases where affective disorders first appeared at the remote stages of alcoholism (II-III and III stages).

[Significance of personality characteristics for the clinical picture and treatment of alcoholism].

The authors examined 118 patients with chronic alcoholism. Taking into consideration the typological personality traits all the patients were divided into 3 groups: cycloid (39 cases), asthenical (41 cases) and hystero-explosive (38 cases). Each group was characterized by distinct clinical traits of alcoholism in their separate symptoms, as well as in the development of the disease as a whole.

[Study of smallpox vaccine virus distribution in the body of rabbits following oral immunization].

Virological and immunofluorescent methods were applied to the study of the distribution of the smallpox vaccine virus in the organs and tissues of rabbits immunized orally. It appeared that the vaccinal process developed with a predominant localization of the antigen in the regional (in respect to the site of administration) lymph nodes; the virus was revealed in the cell cytoplasm.