Nadia Bou Ali shows how a curious relationship was forged between language and politics, one driven both by a desire for modernity and anxiety about it.
Display omitted
In-vitro dissolution testing of pharmaceutical formulations has been used as a quality control test for many years. At early drug product development, in vivo predictive dissolution ...testing can be used for guidance in the rational selection of candidate formulations that best fit the desired in vivo dissolution characteristics. At present, the most widely applied dissolution media are phosphate-based buffers and, in some cases, the result of dissolution tests performed in such media have demonstrated reasonable/acceptable IVIVCs. However, the presence of phosphates in human GI luminal fluids is insignificant, which makes the use of such media poorly representative of the in vivo environment. The gastrointestinal lumen has long been shown to be buffered by bicarbonate. Hence, much interest in the development of suitable biorelevant in vitro dissolution media based on bicarbonate buffer systems has evolved. However, there are inherent difficulties associated with these buffers, such as maintaining the pH throughout the dissolution test, as CO2 tends to leave the system. Various mathematical models have been proposed to analyze bicarbonate buffers and they are discussed in this review. Approaches such as using simpler buffer systems instead of bicarbonate have been proposed as surrogate buffers to produce an equivalent buffer effect on drug dissolution on a case-by-case basis. There are many drawbacks related to simpler buffers systems including their poor in vivo predictability. Considerable discrepancies between phosphate and bicarbonate buffer dissolution results have been reported for certain dosage forms, e.g. enteric coated formulations. The role and need of bicarbonate-based buffers in quality control testing requires scientific analysis. This review also encompasses on the use of bicarbonate-based buffers as a potentially in vivo predictive dissolution medium for enteric coated dosage forms.
Nanoemulsion has the potential to overcome several disadvantages in drug formulation. Loading poor water-soluble drugs in the appropriate nanoemulsions enhances their wettability and/or solubility. ...Consequently, this improves their pharmacokinetics and pharmacodynamics by different routes of administration. Associated with the optimum nanodroplets size or even combined with key components, the droplets act as a reservoir of drugs, enabling nanoemulsion to be multifunctional platform to treat diverse diseases. A number of important advantages, which comprise nanoemulsion attributes, such as efficient drug release with appropriate rate, prolonged efficacy, drug uptake control, low side effects and drug protection properties from enzymatic or oxidative processes, have been reported in last decade. The high flexibility of nanoemulsion includes also a variety of manufacturing process options and a combination of widely assorted components such as surfactants, liquid lipids or even drug-conjugates. These features provide alternatives for designing innovative nanoemulsions aiming at high-value applications. This review presents the challenges and prospects of different nanoemulsion types and its application. The drug interaction with the components of the formulation, as well as the drug mechanistic interaction with the biological environment of different routes of administration are also presented.
The uniqueness of structure and physiology of the lymphatic system make it challenging to delineate all its contributions in the maintenance of our health. However, in the past two decades, the ...understanding of the importance of the function of this system has evolved and more appreciation has been drawn to the distinctive role it plays in health and disease. The lymphatic system has been linked to the pathophysiology of numerous ailments including cancer, various metabolic diseases, inflammatory conditions, and infections. Moreover, it has also been revealed that lymphatic targeted formulations can enhance the delivery of drugs through the lymphatic system to the bloodstream, bypassing the hepatic first-pass metabolism if taken orally, thus increasing the bioavailability, and improving the pharmacokinetic and toxicological profiles in general. Engineering lymphotropic preparations requires the understanding of many factors, the most important one being that of the physiological environment which they will encounter. Therefore, in this review, we detail the basic structure of the lymphatic system, then highlight the therapeutic and the pharmacokinetic benefits of drug delivery into the lymphatic system. The criteria for drugs and formulations used for lymphotropic delivery are also detailed with a contemporary overview of various studies undertaken in this field.
Development of cationic nanocrystals for ocular delivery Romero, Gregori B.; Keck, Cornelia M.; Müller, Rainer H. ...
European journal of pharmaceutics and biopharmaceutics,
October 2016, 2016-Oct, 2016-10-00, 20161001, Volume:
107
Journal Article
Peer reviewed
Display omitted
A cationic nanocrystal formulation containing dexamethasone acetate nanocrystals (0.05%) and polymyxin B (0.10%) for ophthalmic application was produced using a self-developed small ...scale method for wet bead milling. The formulation developed offers the advantage of increased saturation solubility of the drug (due to the nano-size of the crystals) and increased residence time in the eye (due to small size and increased mucoadhesion by the cationic charge) resulting ultimately in potential increased bioavailability. Characterization of the nanosuspensions by photon correlation spectroscopy (PCS) and transmission electron microscopy showed that the production method was successful in achieving dexamethasone crystals in the range of about 200–250nm. The physical stabilization of the nanocrystals and generation of the positive charge were realized by using cetylpyridinium chloride (CPC) and benzalkonium chloride (BAC) at the concentration of 0.01%. In contrast to other cationic excipients, they are regulatorily accepted due to their use as preservatives. The drug polymyxin B also contributed to the positive charge. Positive zeta potentials in the range +20 to +30mV were achieved. Isotonicity was adjusted using NaCl and non-ionic excipients (glycerol, sorbitol, dextrose). Physical and chemical stabilities were monitored for a period of 6months at room temperature, 5°C and 40°C. Particle size of the bulk population assessed by PCS remained practically unchanged over 6months of storage for the various formulations without isotonicity agents, and for the CPC-containing formulations with non-ionic isotonicity excipients. The chemical content also proved stable after 6months for all 3 temperatures evaluated. In vitro investigation of mucoadhesion was tested using mucin solutions at different concentrations, and the generated negative zeta potential was used as a measure of the interaction. The zeta potential reversed to about −15mV, indicating distinct interaction. The results show the potential of increased mucoadhesion of such cationic nanocrystals compared to standard eye drop formulations. The positively charged nanocrystal formulation also showed no in vitro cytotoxicity as assessed on fibroblast cell culture. In summary, 3 formulation candidates were identified being a promising alternative for ocular delivery with increased performance compared to what is presently available.
Engaging two influential, contemporaneous, and yet heterogeneous bodies of thought, Lacan and Foucault, the authors chart distinct trajectories at the peak of French structuralism whose comparison is ...crucial to understanding the contours and stakes of critical theory today. Although these two thinkers have had a number of direct encounters, this volume seeks to stage another encounter in the present, which grounds their divergences and confluences in relationship to the topics of sexuality, the theory of the subject, history and historicism, scientific formalization, and ultimately politics.
The lymphatic system plays a crucial role in the absorption of lipophilic drugs, making it an important route for drug delivery. In this study, an in vitro model using Intralipid® was developed to ...investigate the lymphatic uptake of drugs. The model was validated using cannabidiol, halofantrine, quercetin, and rifampicin. Remarkably, the uptake of these drugs closely mirrored what would transpire in vivo. Furthermore, adding peanut oil to the model system significantly increased the lymphatic uptake of rifampicin, consistent with meals containing fat stimulating lymphatic drug uptake. Conversely, the inclusion of pluronic L-81 was observed to inhibit the lymphatic uptake of rifampicin in the model. This in vitro model emerges as a valuable tool for investigating and predicting drug uptake via the lymphatic system. It marks the first phase in developing a physiologically based predictive tool that can be refined further to enhance the precision of drug interaction predictions with chylomicrons and their subsequent transport via the lymphatic system. Moreover, it can be employed to explore innovative drug formulations and excipients that either enhance or hinder lymphatic drug uptake. The insights gained from this study have significant implications for advancing drug delivery through the lymphatic system.
Currently, the use of Traditional Chinese Medicine (TCM) for healthy living in daily practice is widely accepted across the world. However, not much attention has been paid to the particular ...characteristics of TCM “pills”, one of the classic dosage forms in TCM. For a better understanding, this review was undertaken to provide a modern pharmaceutical overview of pills. Over many centuries, pills have been developed in different types (honeyed pill, water-honeyed pill, watered pill, pasted pill, waxed pill, concentrated pill, and dripping pill) to achieve varying intended TCM release patterns. It suggests that knowledge relating to the impact of binders and excipients on drug release from TCM pills can be traced back to before dissolution testing was invented. Therefore, although Pills may be considered as an ancient and outdated dosage form compared to current drug delivery systems, they have surprisingly modern pharmaceutical properties that is highlighted in this article. In addition, this review found that the quality control standards for TCM pill are globally substantially different. Hence, greater effort should be taken to establish an internationally harmonized and proper standard to safeguard the quality of this dosage form and to ensure the alignment with TCM use.
...against the rise of the Effendiyya as bearers of national mythology, the surrealist group "opposed the conflation of art with national sentiment" (47). According to the author, the group's works ...during the time reacted to the devastating consequences of the war in Egypt and beyond, and are testaments of a generation "consumed by the overwhelming proximity of anguish and death," reflected in the haunting depictions of "broken bodies and desolate wastelands" (85). Bardaouil argues that what Henein adds to the two fundamental tenants of surrealism—the rejection of art for art's sake, and the rejection of a distance between art and political propaganda—is an unlocking of the "spiritual, imaginative, irrational and infinite forces behind creation" in order to "exercise a tangible effect within the derivative, rational and finite realm of the real" (124). According to Bardaouil, the group—in its transformation of the term surrealist and its refusal to fall under one definition of it, and in its differences from both French Marxist surrealism and English anarchist paradigms—"reflects a process of metamorphosis by which the group had no fear to operate beyond the confinements of a fixed intellectual position or defined movement.
Drug absorption via chylomicrons holds significant implications for both pharmacokinetics and pharmacodynamics. However, a mechanistic understanding of predicting in vivo intestinal lymphatic uptake ...remains largely unexplored. This study aimed to delve into the intestinal lymphatic uptake of drugs, investigating both enhancement and inhibition using various excipients through our previously established in vitro model. It also examined the applicability of the model by assessing the lymphatic uptake enhancement of a lymphotropic formulation with linoleoyl polyoxyl-6 glycerides using the same model. The model successfully differentiated among olive, sesame, and peanut oils in terms of lymphatic uptake. However, it did not distinguish between oils containing long-chain fatty acids and coconut oil. Coconut oil, known for its abundance of medium-chain fatty acids, outperformed other oils. This heightened uptake was attributed to the superior emulsification of this oil in artificial chylomicron media due to its high content of medium-chain fatty acids. Additionally, the enhanced uptake of the tested formulation with linoleoyl polyoxyl-6 glycerides underscored the practical applicability of this model in formulation optimization. Moreover, data suggested that increasing the zeta potential of Intralipid® using sodium lauryl sulfate (SLS) and decreasing it using (+/−) chloroquine led to enhanced and reduced uptake in the in vitro model, respectively. These findings indicate the potential influence of the zeta potential on intestinal lymphatic uptake in this model, though further research is needed to explore the possible translation of this mechanism in vivo.
PDF
