A dual pH and microbiota-triggered coating (Phloral™) for fail-safe colonic drug release

Varum, Felipe; Freire, Ana Cristina; Fadda, Hala M.; Bravo, Roberto; Basit, Abdul W.

doi:10.1016/j.ijpharm.2020.119379

Cited by 74 publications

(49 citation statements)

References 77 publications

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“…Specifically, ulcerative colitis is characterised by inflammation of the colon and the rectum. Despite being an inflammatory condition of the distal gastrointestinal tract, the majority of efforts for new treatments have revolved around the development of oral therapies [3] , [4] , [5] . However, oral delivery in ulcerative colitis is challenging as potentially only a fraction of the administered drug might reach the intended site of action.…”

Section: Introductionmentioning

confidence: 99%

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Seoane-Viaño

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Luzardo-Álvarez

et al. 2021

Asian Journal of Pharmaceutical Sciences

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Ulcerative colitis is a global health problem, affecting millions of individuals worldwide. As an inflammatory condition localised in the large intestine, rectal delivery of immunosuppressive therapies such as tacrolimus is a promising strategy to maximise drug concentration at the site of action whilst minimising systemic side effects. Here, for the first time, self-supporting 3D-printed tacrolimus suppositories were prepared without the aid of moulds using a pharmaceutical semi-solid extrusion (SSE) 3D printer. The suppositories were printed vertically in three different sizes using combinations of two lipid pharmaceutical excipients (Gelucire 44/14 or Gelucire 48/16) and coconut oil. Although both suppository formulations had the appropriate viscosity characteristics for printing, the Gel 44 formulation required less energy and force for extrusion compared to the Gel 48 system. The Gel 44 disintegrated more rapidly but released tacrolimus more slowly than the Gel 48 suppositories. Although the tacrolimus release profiles were significantly different, both suppository systems released more than 80% drug within 120 min. DSC and XRD analysis was inconclusive in determining the solid-state properties of the drug in the suppositories. In summary, this article reports on the fabrication of 3D printed self-supporting suppositories to deliver personalised doses of a narrow therapeutic index drug, with potential benefits for patients with ulcerative colitis.

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Section: Introductionmentioning

confidence: 99%

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Seoane-Viaño

Ong

Luzardo-Álvarez

et al. 2021

Asian Journal of Pharmaceutical Sciences

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“…Therefore, the intestinal pH is critical for drug solubility and affects the absorption and bioavailability, especially of oral drugs. In addition, enteric-coated drug delivery is increasingly being investigated [3][4][5][6]. Polymers dissolve depending on the pH and are used for modified or targeted drug release.…”

Section: Introductionmentioning

confidence: 99%

Measurement of the Intestinal pH in Mice under Various Conditions Reveals Alkalization Induced by Antibiotics

et al. 2021

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The intestinal pH can greatly influence the stability and absorption of oral drugs. Therefore, knowledge of intestinal pH is necessary to understand the conditions for drug delivery. This has previously been measured in humans and rats. However, information on intestinal pH in mice is insufficient despite these animals being used often in preclinical testing. In this study, 72 female ICR mice housed in SPF (specific pathogen-free) conditions were separated into nine groups to determine the intestinal pH under conditions that might cause pH fluctuations, including high-protein diet, ageing, proton pump inhibitor (PPI) treatment, several antibiotic treatment regimens and germ-free mice. pH was measured in samples collected from the ileum, cecum and colon, and compared to control animals. An electrode, 3 mm in diameter, enabled accurate pH measurements with a small amount of gastrointestinal content. Consequently, the pH values in the cecum and colon were increased by high-protein diet, and the pH in the ileum was decreased by PPI. Drastic alkalization was induced by antibiotics, especially in the cecum and colon. The alkalized pH values in germ-free mice suggested that the reduction in the intestinal bacteria caused by antibiotics led to alkalization. Alkalization of the intestinal pH caused by antibiotic treatment was verified in mice. We need further investigations in clinical settings to check whether the same phenomena occur in patients.

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“…91,92 For example, fermentable carbohydrate coatings have been developed for accurate colonic drug delivery. 93,94 Supplied with information on a drug compound, ML can quickly and accurately assess formulation options without bias. 95 Due to the complex nature of formulation science, deep ML techniques are especially useful.…”

Section: Figurementioning

confidence: 99%

Harnessing machine learning for development of microbiome therapeutics

et al. 2021

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The last twenty years of seminal microbiome research has uncovered microbiota's intrinsic relationship with human health. Studies elucidating the relationship between an unbalanced microbiome and disease are currently published daily. As such, microbiome big data have become a reality that provide a mine of information for the development of new therapeutics. Machine learning (ML), a branch of artificial intelligence, offers powerful techniques for big data analysis and predictionmaking, that are out of reach of human intellect alone. This review will explore how ML can be applied for the development of microbiome-targeted therapeutics. A background on ML will be given, followed by a guide on where to find reliable microbiome big data. Existing applications and opportunities will be discussed, including the use of ML to discover, design, and characterize microbiome therapeutics. The use of ML to optimize advanced processes, such as 3D printing and in silico prediction of drug-microbiome interactions, will also be highlighted. Finally, barriers to adoption of ML in academic and industrial settings will be examined, concluded by a future outlook for the field.

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A dual pH and microbiota-triggered coating (Phloral™) for fail-safe colonic drug release

Abstract: A dual pH and microbiota-triggered coating (Phloral TM ) for fail-safe colonic drug release,

Cited by 74 publications

References 77 publications

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

3D printed tacrolimus suppositories for the treatment of ulcerative colitis

Measurement of the Intestinal pH in Mice under Various Conditions Reveals Alkalization Induced by Antibiotics

Harnessing machine learning for development of microbiome therapeutics

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