scholarly journals Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 995
Author(s):  
Manali Banerjee ◽  
Blair Brettmann
Keyword(s):  
Crystal Size ◽  
Water Solubility ◽  
Pharmaceutical Research ◽  
Oral Dosage ◽  
Free Energies ◽  
Pharmaceutical Ingredients ◽  
Surface Functionality ◽  
Dissolution Properties ◽  
Combined Crystallization ◽  
Oral Dosage Forms

Poor water solubility is one of the major challenges to the development of oral dosage forms containing active pharmaceutical ingredients (APIs). Polymorphism in APIs leads to crystals with different surface wettabilities and free energies, which can lead to different dissolution properties. Crystal size and habit further contribute to this variability. An important focus in pharmaceutical research has been on controlling the drug form to improve the solubility and thus bioavailability of APIs. In this regard, heterogeneous crystallization on surfaces and crystallization under confinement have become prominent forms of controlling polymorphism and drug crystal size and habits; however there has not been a thorough review into the emerging field of combining these approaches to control crystallization. This tutorial-style review addresses the major advances that have been made in controlling API forms using combined crystallization methods. By designing templates that not only control the surface functionality but also enable confinement of particles within a porous structure, these combined systems have the potential to provide better control over drug polymorph formation and crystal size and habit. This review further provides a perspective on the future of using a combined crystallization approach and suggests that combining surface templating with confinement provides the advantage of both techniques to rationally design systems for API nucleation.

scholarly journals Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 190 ◽  
Author(s):  
Guillaume Binson ◽  
Karine Beuzit ◽  
Virginie Migeot ◽  
Léa Marco ◽  
Barbara Troussier ◽  
...  
Keyword(s):  
Water Solubility ◽  
Storage Condition ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Pharmaceutical Ingredients ◽  
Physicochemical Stability ◽  
Oral Liquid ◽  
Reliable Solution ◽  
Physical And Chemical ◽  
Harmful Excipients

Dexamethasone, hydrochlorothiazide, spironolactone, and phenytoin are commonly used in neonates, but no age-appropriate formulation containing these active pharmaceutical ingredients (APIs) is commercially available. Thus, pharmaceutical compounding of the liquid oral dosage form is required to enable newborn administration. A problem common to the compounded preparations described in the literature is that they include potentially harmful excipients (PHEs). Therefore, the aim of this study was to evaluate the feasibility of compounding oral liquid dosage forms free of PHE, containing dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone and to assess their physicochemical stability. Due to the poor water solubility of the targeted APIs, oral suspensions were compounded using Syrspend® SF-PH4 Dry, a suspending vehicle free of PHE. Four HPLC coupled to UV spectrometry (HPLC-UV) stability-indicating methods were developed and validated according to international guidelines to assay the strength of the targeted APIs. Whatever storage condition was used (5 ± 3 °C or 22 ± 4 °C), no significant degradation of API occurred in compounded oral suspensions. Overall, the results attest to the physical and chemical stability of the four oral liquid dosage forms over 60 days under regular storage temperatures. Finally, the use of the proposed oral suspensions provides a reliable solution to reduce the exposure of children to potentially harmful excipients.

scholarly journals 3D Printed Pellets (Miniprintlets): A Novel, Multi-Drug, Controlled Release Platform Technology

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 148 ◽  
Author(s):  
Atheer Awad ◽  
Fabrizio Fina ◽  
Sarah Trenfield ◽  
Pavanesh Patel ◽  
Alvaro Goyanes ◽  
...  
Keyword(s):  
Drug Release ◽  
Ethyl Cellulose ◽  
Selective Laser Sintering ◽  
Three Dimensional ◽  
Single Step ◽  
Oral Dosage ◽  
Three Dimensional Printing ◽  
Pharmaceutical Ingredients ◽  
3D Printed ◽  
Oral Dosage Forms

Selective laser sintering (SLS) is a single-step three-dimensional printing (3DP) process that can be leveraged to engineer a wide array of drug delivery systems. The aim of this work was to utilise SLS 3DP, for the first time, to produce small oral dosage forms with modified release properties. As such, paracetamol-loaded 3D printed multiparticulates, termed miniprintlets, were fabricated in 1 mm and 2 mm diameters. Despite their large surface area compared with a conventional monolithic tablet, the ethyl cellulose-based miniprintlets exhibited prolonged drug release patterns. The possibility of producing miniprintlets combining two drugs, namely paracetamol and ibuprofen, was also investigated. By varying the polymer, the dual miniprintlets were programmed to achieve customised drug release patterns, whereby one drug was released immediately from a Kollicoat Instant Release matrix, whilst the effect of the second drug was sustained over an extended time span using ethyl cellulose. Herein, this work has highlighted the versatility of SLS 3DP to fabricate small and intricate formulations containing multiple active pharmaceutical ingredients with distinct release properties.

scholarly journals Drug Solubility Enhancement through the Preparation of Multicomponent Organic Materials: Eutectics of Lovastatin with Carboxylic Acids

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 112 ◽  
Author(s):  
Andrea Araya-Sibaja ◽  
José Vega-Baudrit ◽  
Teodolito Guillén-Girón ◽  
Mirtha Navarro-Hoyos ◽  
Silvia Cuffini
Keyword(s):  
Carboxylic Acids ◽  
Water Solubility ◽  
Pharmaceutical Product ◽  
Solubility Enhancement ◽  
Oral Dosage ◽  
Scanning Calorimetry ◽  
Molar Ratios ◽  
Product Formulation ◽  
Eutectic Systems ◽  
Oral Dosage Forms

Lovastatin (LOV) is a drug used to treat hypercholesterolemia. Recent studies have identified its antioxidant effects and potential use in the treatment of some types of cancer. However, the low bioavailability related to its poor water solubility limits its use in solid oral dosage forms. Therefore, to improve the solubility of LOV three eutectic systems of LOV with the carboxylic acids benzoic (BEN), salicylic (SAL) and cinnamic (CIN) were obtained. Both binary phase and Tammann diagrams were constructed using differential scanning calorimetry (DSC) data of mixtures prepared from 0.1 to 1.0 molar ratios. Binary mixtures and eutectics were prepared by liquid-assisted grinding. The eutectics were further characterized by DSC and powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The LOV-BEN, LOV-SAL and LOV-CIN system formed a eutectic at an LOV mole fraction of 0.19, 0.60 and 0.14, respectively. The systems exhibited improvements in LOV solubility, becoming more soluble by five-fold in the LOV-SAL system and approximately four-fold in the other two systems. Considering that the solubility enhancements and the carboxylic acids used are generally recognized as safe by the U.S. Food and Drug Administration (FDA), the LOV eutectic systems are promising materials to be used in a solubility enhancement strategy for pharmaceutical product formulation.

scholarly journals Photocurable Bioinks for the 3D Pharming of Combination Therapies

Polymers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1372 ◽  
Author(s):  
Giovanny Acosta-Vélez ◽  
Chase Linsley ◽  
Timothy Zhu ◽  
Willie Wu ◽  
Benjamin Wu
Keyword(s):  
3D Printing ◽  
High Performance ◽  
Oral Dosage ◽  
Combination Therapies ◽  
Drug Synergy ◽  
Pharmaceutical Ingredients ◽  
Release Analysis ◽  
Poly Ethylene ◽  
Oral Dosage Forms ◽  
Binder Jetting

Combination therapies mediate drug synergy to improve treatment efficacy and convenience, leading to higher levels of compliance. However, there are challenges with their manufacturing as well as reduced flexibility in dosing options. This study reports on the design and characterization of a polypill fabricated through the combination of material jetting and binder jetting for the treatment of hypertension. The drugs lisinopril and spironolactone were loaded into hydrophilic hyaluronic acid and hydrophobic poly(ethylene glycol) (PEG) photocurable bioinks, respectively, and dispensed through a piezoelectric nozzle onto a blank preform tablet composed of two attachable compartments fabricated via binder jetting 3D printing. The bioinks were photopolymerized and their mechanical properties were assessed via Instron testing. Scanning electron microscopy (SEM) was performed to indicate morphological analysis. The polypill was ensembled and drug release analysis was performed. Droplet formation of bioinks loaded with hydrophilic and hydrophobic active pharmaceutical ingredients (APIs) was achieved and subsequently polymerized after a controlled dosage was dispensed onto preform tablet compartments. High-performance liquid chromatography (HPLC) analysis showed sustained release profiles for each of the loaded compounds. This study confirms the potential of material jetting in conjunction with binder jetting techniques (powder-bed 3D printing), for the production of combination therapy oral dosage forms involving both hydrophilic and hydrophobic drugs.

scholarly journals Application of Permeation Enhancers in Oral Delivery of Macromolecules: An Update

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 41 ◽  
Author(s):  
Sam Maher ◽  
David Brayden ◽  
Luca Casettari ◽  
Lisbeth Illum
Keyword(s):  
Oral Delivery ◽  
State Of The Art ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Active Pharmaceutical Ingredients ◽  
Permeation Enhancers ◽  
Pharmaceutical Ingredients ◽  
Current State ◽  
Oral Formulations ◽  
Oral Dosage Forms

The application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach. Several hundred compounds have been shown to alter the epithelial barrier, and although the research emphasis has broadened to encompass a role for nanoparticle approaches, PEs represent a key constituent of conventional oral formulations that have progressed to clinical testing. In this review, we highlight promising PEs in early development, summarize the current state of the art, and highlight challenges to the translation of PE-based delivery systems into safe and effective oral dosage forms for patients.

Patent landscape of pediatric-friendly oral dosage forms and administration devices

2021 ◽  
pp. 1-23
Author(s):  
Christina Karavasili ◽  
Angelos Gkaragkounis ◽  
Dimitrios G. Fatouros
Keyword(s):  
Dosage Forms ◽  
Oral Dosage ◽  
Patent Landscape ◽  
Oral Dosage Forms

scholarly journals Multi-Analytical Framework to Assess the In Vitro Swallowability of Solid Oral Dosage Forms Targeting Patient Acceptability and Adherence

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 411
Author(s):  
Abdul Latif Ershad ◽  
Ali Rajabi-Siahboomi ◽  
Shahrzad Missaghi ◽  
Daniel Kirby ◽  
Afzal Rahman Mohammed
Keyword(s):  
Hydroxypropyl Methylcellulose ◽  
Analytical Framework ◽  
Dosage Forms ◽  
Oral Dosage ◽  
Surface Erosion ◽  
World Population ◽  
Swallowing Problems ◽  
Solid Oral Dosage Forms ◽  
Oral Dosage Forms

A lack of effective intervention in addressing patient non-adherence and the acceptability of solid oral dosage forms combined with the clinical consequences of swallowing problems in an ageing world population highlight the need for developing methods to study the swallowability of tablets. Due to the absence of suitable techniques, this study developed various in vitro analytical tools to assess physical properties governing the swallowing process of tablets by mimicking static and dynamic stages of time-independent oral transitioning events. Non-anatomical models with oral mucosa-mimicking surfaces were developed to assess the swallowability of tablets; an SLA 3D printed in vitro oral apparatus derived the coefficient of sliding friction and a friction sledge for a modified tensometer measured the shear adhesion profile. Film coat hydration and in vitro wettability was evaluated using a high-speed recording camera that provided quantitative measurements of micro-thickness changes, simulating static in vivo tablet–mucosa oral processing stages with artificial saliva. In order to ascertain the discriminatory power and validate the multianalytical framework, a range of commonly available tablet coating solutions and new compositions developed in our lab were comparatively evaluated according to a quantitative swallowability index that describes the mathematical relationship between the critical physical forces governing swallowability. This study showed that the absence of a film coat significantly impeded the ease of tablet gliding properties and formed chalky residues caused by immediate tablet surface erosion. Novel gelatin- and λ-carrageenan-based film coats exhibited an enhanced lubricity, lesser resistance to tangential motion, and reduced stickiness than polyvinyl alcohol (PVA)–PEG graft copolymer, hydroxypropyl methylcellulose (HPMC), and PVA-coated tablets; however, Opadry® EZ possessed the lowest friction–adhesion profile at 1.53 a.u., with the lowest work of adhesion profile at 1.28 J/mm2. For the first time, the in vitro analytical framework in this study provides a fast, cost-effective, and repeatable swallowability ranking method to screen the in vitro swallowability of solid oral medicines in an effort to aid formulators and the pharmaceutical industry to develop easy-to-swallow formulations.

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