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Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving.

ABSTRACT: This contribution reviews the efforts of many scientists around the world to discover and structurally characterize olanzapine crystal forms, clearing up inconsistencies in the scientific and patent literature and highlighting the challenges in identifying new forms amidst 60+ known polymorphs and solvates. Owing to its remarkable solid-state chemistry, olanzapine has emerged over the last three decades as a popular tool compound for developing new experimental and computational methods for enhanced molecular level understanding of solid-state structure, form diversity and crystallization outcomes. This article highlights the role of olanzapine in advancing the fundamental understanding of crystal forms, interactions within crystal structures, and growth units in molecular crystallization, as well as influencing the way in which drugs are developed today.

SUBMITTER: Reutzel-Edens SM

PROVIDER: S-EPMC7642794 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving.

Reutzel-Edens Susan M SM Bhardwaj Rajni M RM

IUCrJ 20201003 Pt 6

This contribution reviews the efforts of many scientists around the world to discover and structurally characterize olanzapine crystal forms, clearing up inconsistencies in the scientific and patent literature and highlighting the challenges in identifying new forms amidst 60+ known polymorphs and solvates. Owing to its remarkable solid-state chemistry, olanzapine has emerged over the last three decades as a popular tool compound for developing new experimental and computational methods for enha ...[more]

PMID: 33209310

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Project description:Interactions between pharmaceutical companies and healthcare providers are increasingly scrutinized by academics, professionals, media, and politicians. Most empirical studies and professional guidelines focus on unilateral donor-recipient types of interaction and overlook, or fail to distinguish between, more reciprocal types of interaction. However, the degree of goal alignment and potential for value creation differs in these two types of interactions. Failing to differentiate between these two forms of interaction between pharmaceutical companies and healthcare providers could thus lead to biased conclusions regarding their desirability. This study reviews the empirical literature regarding the effects of bilateral forms of interactions between pharmaceutical companies and healthcare providers in order to explore their effects.We searched two medical databases (i.e. PubMed and Cochrane Library) and one business database (i.e. EBSCO) for empirical, peer-reviewed articles concerning any type of bilateral interaction between pharmaceutical companies and healthcare providers. We included quantitative articles which were written in English and published between January 1st, 2000 and October 31st, 2016, and where the title or abstract included a combination of synonyms of the following keywords: pharmaceutical companies, healthcare providers, interaction, and effects.Our search results yielded 10 studies which were included in our analysis. These studies focused on either research-oriented interaction or on education-oriented interaction. The included studies reported various outcomes of interaction such as prescribing behavior, ethical dilemmas, and research output. Regardless of the type of interaction, the studies either reported no significant effects or ambivalent outcomes such as affected clinical practice or ethical issues.The effects of bilateral interactions reported in the literature are similar to those reported in studies concerning unilateral interactions. The theoretical notion that bilateral interactions between pharmaceutical companies and healthcare providers have different effects given their increased level of goal alignment thus does not seem to hold. However, most of the empirical studies focus on intermediary, provider-level, outcomes such as altered prescribing behavior. Outcomes at the health system level such as overall costs and quality of care are overlooked. Further research is necessary in order to disentangle various forms of value created by different types of interactions between pharmaceutical companies and healthcare providers.

Project description:BackgroundWhen males are selective, they can either reject low-quality females or adjust their reproductive investment in response to traits that indicate female quality (e.g., body size or condition). According to the differential allocation hypothesis, males increase their reproductive investment when paired with high-quality females (positive differential allocation) or increase their reproductive investment when paired with low-quality females (negative differential allocation). This hypothesis has been proposed for monogamous species with biparental care, and most empirical studies focus on birds. Here we used the polygamous spider Paratrechalea ornata, in which males offer prey wrapped in silk as nuptial gifts, to test whether males adjust their reproductive investment in gift size, pre-copulatory and copulatory courtship, and sperm transfer in response to female body condition.ResultsMales exposed to females in good body condition added more flies to the gift, stimulated these females longer with abdominal touches during pre-copulatory courtship, and had longer pedipalp insertions than males exposed to females in poor body condition. Female condition affected neither silk investment in nuptial gift wrapping nor the quantity of sperm transferred by males. Finally, females in good body condition oviposited faster after copulation and laid more eggs than females in poor body condition.ConclusionsWe provide experimental evidence that males of a gift-giving spider exhibit positive differential allocation in three key aspects of their reproductive investment: the size of the nutritious gift, duration of pre-copulatory courtship, and duration of pedipalp insertions, which is regarded as a form of copulatory courtship in spiders. This positive differential allocation is likely associated with the benefits of copulating with females in good body condition. These females are more fecund and oviposit faster after copulation than females in poor body condition, which under natural field conditions probably reduces the risk of multiple matings and thus the level of sperm competition faced by the males. As a final remark, our findings indicate that the hypothesis of differential allocation also applies to species with a scramble competition mating system, in which males heavily invest in nuptial gift construction, but not in parental care.

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Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving.

Publications

Crystal forms in pharmaceutical applications: olanzapine, a gift to crystal chemistry that keeps on giving.

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