Polymer-mediated drug supersaturation - a spotlight on the interplay between phase-separated amorphous drug colloids and dissolved molecules

2021 ◽  
Author(s):  
Ozan Hirlak ◽  
Sabine Dieluweit ◽  
Rudolf Merkel ◽  
Karl G. Wagner
Keyword(s):  
Amorphous Drug

Amorphous Drug Delivery Systems: Molecular Aspects, Design, and Performance

2004 ◽  
Vol 21 (3) ◽  
pp. 133-193 ◽  
Author(s):  
Aditya Mohan Kaushal ◽  
Piyush Gupta ◽  
Arvind Kumar Bansal
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Molecular Aspects ◽  
And Performance ◽  
Amorphous Drug

Amorphous and Crystalline Particulates: Challenges and Perspectives in Drug Delivery

2017 ◽  
Vol 23 (3) ◽  
pp. 350-361 ◽  
Author(s):  
Hisham Al-Obaidi ◽  
Mridul Majumder ◽  
Fiza Bari
Keyword(s):  
Crystal Engineering ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Chemical Properties ◽  
Pharmaceutical Product ◽  
Water Soluble ◽  
Amorphous Form ◽  
Physico Chemical ◽  
Water Soluble Drugs ◽  
Amorphous Drug

Crystalline and amorphous dispersions have been the focus of academic and industrial research due to their potential role in formulating poorly water-soluble drugs. This review looks at the progress made starting with crystalline carriers in the form of eutectics moving towards more complex crystalline mixtures. It also covers using glassy polymers to maintain the drug as amorphous exhibiting higher energy and entropy. However, the amorphous form tends to recrystallize on storage, which limits the benefits of this approach. Specific interactions between the drug and the polymer may retard this spontaneous conversion of the amorphous drug. Some studies have shown that it is possible to maintain the drug in the amorphous form for extended periods of time. For the drug and the polymer to form a stable mixture they have to be miscible on a molecular basis. Another form of solid dispersions is pharmaceutical co-crystals, for which research has focused on understanding the chemistry, crystal engineering and physico-chemical properties. USFDA has issued a guidance in April 2013 suggesting that the co-crystals as a pharmaceutical product may be a reality; but just not yet! While some of the research is still oriented towards application of these carriers, understanding the mechanism by which drug-carrier miscibility occurs is also covered. Within this context is the use of thermodynamic models such as Flory-Huggins model with some examples of studies used to predict miscibility.

Exploiting Kinetic Solubility Differences for Low Level Detection of Crystallinity in Amorphous Drug Formulations

2020 ◽  
Vol 16 (5) ◽  
pp. 529-538
Author(s):  
Gregory K. Webster ◽  
Cynthia A. Pommerening ◽  
Whitney W. Harman ◽  
Mathew A. Gragg ◽  
Jian-Hwa Han ◽  
...  
Keyword(s):  
Dosage Form ◽  
Amorphous State ◽  
Analytical Techniques ◽  
Drug Level ◽  
Drug Substance ◽  
Phase Iii ◽  
Drug Formulations ◽  
Total Recovery ◽  
Amorphous Drug ◽  
Kinetic Solubility

Background: Enabling formulations have been implemented by the pharmaceutical industry as an effective tool for keeping Active Pharmaceutical Ingredient (API) in an amorphous state. Upon dosing in the amorphous state, many drugs which fail to demonstrate bioactivity due to the limited solubility and bioavailability of their crystalline form become bioavailable. Purpose: The analytical techniques use today for crystallinity detection are challenged by the sensitivity and robustness needed to achieve a 5% quantitation limit in low dose drug products. Our laboratory has developed a novel procedure capable of meeting this sensitivity and selectivity requirement. This is achieved by exploiting the differences in kinetic solubility of the formulated amorphous and free crystalline forms of API currently being used in dosage form platforms. Methods: Representative amorphous drug formulations were prepared and spiked with varying levels of crystalline drug substances to evaluate the selectivity and recovery of the crystalline drug substance from the product formulation. Kinetic solubility testing using a (i) Particle wetting phase, (ii) Particle suspending/erosion phase, (iii) Sampling time point and (iv) A total recovery determination for the drug substance. Results: The method selectively and quantitatively distinguishes crystalline drug substance from amorphous drug substance for samples spiked from 2.5% to 10% of the nominal label concentration of the API in the dosage form matrix. Conclusion: The kinetic solubility approach reported here achieves sensitive crystallinity quantitation for low drug level amorphous drug formulations at levels not yet achieved by complimentary analytical techniques.

Amorphous Drug Nanosuspensions. 3. Particle Dissolution and Crystal Growth

Langmuir ◽  
2007 ◽  
Vol 23 (19) ◽  
pp. 9866-9874 ◽  
Author(s):  
Lennart Lindfors ◽  
Pia Skantze ◽  
Urban Skantze ◽  
Jan Westergren ◽  
Ulf Olsson
Keyword(s):  
Crystal Growth ◽  
Particle Dissolution ◽  
Amorphous Drug

Supersaturating drug delivery systems: The potential of co-amorphous drug formulations

2017 ◽  
Vol 532 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Riikka Laitinen ◽  
Korbinian Löbmann ◽  
Holger Grohganz ◽  
Petra Priemel ◽  
Clare J. Strachan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Drug Formulations ◽  
Amorphous Drug

Amorphous Drug Nanosuspensions. 2. Experimental Determination of Bulk Monomer Concentrations

Langmuir ◽  
2006 ◽  
Vol 22 (3) ◽  
pp. 911-916 ◽  
Author(s):  
Lennart Lindfors ◽  
Sara Forssén ◽  
Pia Skantze ◽  
Urban Skantze ◽  
Anna Zackrisson ◽  
...  
Keyword(s):  
Experimental Determination ◽  
Amorphous Drug

Glass-forming ability of compounds in marketed amorphous drug products

2017 ◽  
Vol 112 ◽  
pp. 204-208 ◽  
Author(s):  
Nicole Wyttenbach ◽  
Martin Kuentz
Keyword(s):  
Glass Forming Ability ◽  
Drug Products ◽  
Glass Forming ◽  
Amorphous Drug

scholarly journals Amorphous Drug-Polymer Salts

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1271
Author(s):  
Xin Yao ◽  
Amy Lan Neusaenger ◽  
Lian Yu
Keyword(s):  
Recent Progress ◽  
Drug Loading ◽  
Salt Formation ◽  
High Drug ◽  
Coated Particles ◽  
Tropical Conditions ◽  
Amorphous Drugs ◽  
Amorphous Drug ◽  
Future Work ◽  
High Drug Loading

Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.

scholarly journals Synthesis of Carbon Onion and Its Application as a Porous Carrier for Amorphous Drug Delivery

Crystals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 281
Author(s):  
Nikhila Miriyala ◽  
Daniel J. Kirby ◽  
Aude Cumont ◽  
Ruoying Zhang ◽  
Baogui Shi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Chemical Nature ◽  
Drug Carrier ◽  
Drug Loading ◽  
Sodium Dodecyl ◽  
Porous Carrier ◽  
Amorphous Form ◽  
Carbon Onion ◽  
Low Cytotoxicity ◽  
Amorphous Drug

Given the great potential of porous carrier-based drug delivery for stabilising the amorphous form of drugs and enhancing dissolution profiles, this work is focussed on the synthesis and application of carbon onion or onion-like carbon (OLC) as a porous carrier for oral amorphous drug delivery, using paracetamol (PA) and ibuprofen (IBU) as model drugs. Annealing of nanodiamonds at 1100 °C produced OLC with a diamond core that exhibited low cytotoxicity on Caco-2 cells. Solution adsorption followed by centrifugation was used for drug loading and results indicated that the initial concentration of drug in the loading solution needs to be kept below 11.5% PA and 20.7% IBU to achieve complete amorphous loading. Also, no chemical interactions between the drug and OLC could be detected, indicating the safety of loading into OLC without changing the chemical nature of the drug. Drug release was complete in the presence of sodium dodecyl sulphate (SDS) and was faster compared to the pure crystalline drug, indicating the potential of OLC as an amorphous drug carrier.

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