Comment on “Trimorphs of a pharmaceutical cocrystal involving two active pharmaceutical ingredients: potential relevance to combination drugs” by S. Aitipamula, P. S. Chow and R. B. H. Tan, CrystEngComm, 2009, 11, 1823

CrystEngComm ◽  
2018 ◽  
Vol 20 (3) ◽  
pp. 370-372 ◽  
Author(s):  
Łukasz Szeleszczuk ◽  
Dariusz Maciej Pisklak ◽  
Monika Zielińska-Pisklak
Keyword(s):  
Detailed Analysis ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Combination Drugs ◽  
Pharmaceutical Cocrystal ◽  
The Stability

This is a commentary on a paper by S. Aitipamula et al. (CrystEngComm, 2009, 11, 1823–1827) on the detailed analysis of the stability of trimorphic cocrystals.

Reply to the ‘Comment on “Trimorphs of a pharmaceutical cocrystal involving two active pharmaceutical ingredients: potential relevance to combination drugs” by S. Aitipamula, P. S. Chow and R. B. H. Tan, CrystEngComm, 2009, 11, 1823’

CrystEngComm ◽  
2018 ◽  
Vol 20 (3) ◽  
pp. 373-374
Author(s):  
Srinivasulu Aitipamula ◽  
Pui Shan Chow ◽  
Reginald B. H. Tan
Keyword(s):  
Lattice Energy ◽  
Previous Article ◽  
Active Pharmaceutical Ingredients ◽  
Energy Calculations ◽  
Pharmaceutical Ingredients ◽  
Combination Drugs ◽  
Pharmaceutical Cocrystal

The inadvertent errors in the lattice energy calculations of the cocrystal polymorphs reported in our previous article were rectified.

Trimorphs of a pharmaceutical cocrystal involving two active pharmaceutical ingredients: potential relevance to combination drugs

CrystEngComm ◽  
2009 ◽  
Vol 11 (9) ◽  
pp. 1823-1827 ◽  
Author(s):  
Srinivasulu Aitipamula ◽  
Pui Shan Chow ◽  
Reginald B. H. Tan
Keyword(s):  
Solid State ◽  
Stable Form ◽  
Active Pharmaceutical Ingredients ◽  
Gentisic Acid ◽  
Pharmaceutical Cocrystals ◽  
Pharmaceutical Ingredients ◽  
Combination Drugs ◽  
Pharmaceutical Cocrystal

The first example of a trimorphic cocrystal involving two active pharmaceutical ingredients, ethenzamide and gentisic acid, is reported; metastable polymorphs convert to the stable form upon solid-state grinding; pharmaceutical cocrystals involving two or more APIs have potential relevance to combination drugs.

scholarly journals Stability Study of Isoniazid and Rifampicin Oral Solutions Using Hydroxypropyl-Β-Cyclodextrin to Treat Tuberculosis in Paediatrics

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 195
Author(s):  
Ana Santoveña-Estévez ◽  
Javier Suárez-González ◽  
Amor R. Cáceres-Pérez ◽  
Zuleima Ruiz-Noda ◽  
Sara Machado-Rodríguez ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Stability Study ◽  
Active Pharmaceutical Ingredients ◽  
Adherence To Treatment ◽  
Pharmaceutical Ingredients ◽  
Antituberculosis Treatment ◽  
Maximum Stability ◽  
Ph Conditions ◽  
The Stability

(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-β-cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% w/v enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 °C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.

scholarly journals Raman and Terahertz Spectroscopic Investigation of Cocrystal Formation Involving Antibiotic Nitrofurantoin Drug and Coformer 4-aminobenzoic Acid

2016 ◽  
Author(s):  
Yong Du ◽  
Qiang Cai ◽  
Jiadan Xue ◽  
Qi Zhang
Keyword(s):  
Solid State ◽  
Spectroscopic Techniques ◽  
Vibrational Modes ◽  
Active Pharmaceutical Ingredients ◽  
Aminobenzoic Acid ◽  
Parent Materials ◽  
Pharmaceutical Development ◽  
Pharmaceutical Ingredients ◽  
Pharmaceutical Cocrystal ◽  
Rich Information

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

Enhancing the stability of active pharmaceutical ingredients by cocrystal strategy

CrystEngComm ◽  
2022 ◽  
Author(s):  
Liyu Liu ◽  
Jian-Rong Wang ◽  
Xuefeng Mei
Keyword(s):  
Active Pharmaceutical Ingredients ◽  
Stability Problems ◽  
Pharmaceutical Ingredients ◽  
The Past ◽  
Scant Attention ◽  
The Stability

Cocrystallization has been recognized as one of the most successful approaches to address stability problems of active pharmaceutical ingredients (APIs) in the past few decades. However, scant attention has been...

scholarly journals Stability of Pharmaceutical Co-Crystals at Humid Conditions Can Be Predicted

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 433
Author(s):  
Heiner Veith ◽  
Maximilian Zaeh ◽  
Christian Luebbert ◽  
Naír Rodríguez-Hornedo ◽  
Gabriele Sadowski
Keyword(s):  
Pharmaceutical Formulations ◽  
Active Pharmaceutical Ingredient ◽  
Storage Conditions ◽  
Pharmaceutical Products ◽  
Active Pharmaceutical Ingredients ◽  
Statistical Associating Fluid Theory ◽  
Pharmaceutical Ingredients ◽  
Soluble Solid ◽  
Fluid Theory ◽  
The Stability

Knowledge of the stability of pharmaceutical formulations against relative humidity (RH) is essential if they are to become pharmaceutical products. The increasing interest in formulating active pharmaceutical ingredients as stable co-crystals (CCs) triggers the need for fast and reliable in-silico predictions of CC stability as a function of RH. CC storage at elevated RH can lead to deliquescence, which leads to CC dissolution and possible transformation to less soluble solid-state forms. In this work, the deliquescence RHs of the CCs succinic acid/nicotinamide, carbamazepine/nicotinamide, theophylline/citric acid, and urea/glutaric acid were predicted using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT). These deliquescence RH values together with predicted phase diagrams of CCs in water were used to determine critical storage conditions, that could lead to CC instability, that is, CC dissolution and precipitation of its components. The importance of CC phase purity on RH conditions for CC stability is demonstrated, where trace levels of a separate phase of active pharmaceutical ingredient or of coformer can significantly decrease the deliquescence RH. The use of additional excipients such as fructose or xylitol was predicted to decrease the deliquescence RH even further. All predictions were successfully validated by stability measurements at 58%, 76%, 86%, 93%, and 98% RH and 25 °C.

scholarly journals How to Achieve High Encapsulation Efficiencies for Macromolecular and Sensitive APIs in Liposomes

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 691
Author(s):  
Kirsten Ullmann ◽  
Gero Leneweit ◽  
Hermann Nirschl
Keyword(s):  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Encapsulation Efficiency ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Bending Modulus ◽  
Vis Spectroscopy ◽  
The Stability ◽  
Very High

This research highlights the capacity of a newly introduced centrifugation process to form liposomes from water-in-fluorocarbon nano-emulsions stabilized with phospholipids to incorporate macromolecular and sensitive active pharmaceutical ingredients (API). The encapsulation efficiency of the produced liposomes, incorporating fluorescein-sodium, bovine serum albumin and fluorecein isothiocyanate dextran as model APIs, is determined by applying Vivaspin® centrifugation filtration and quantified by UV-Vis spectroscopy. It was found that higher densities of the fluorocarbons used as the hydrophobic phase enable a higher encapsulation efficiency and that an efficiency of up to 98% is possible depending on the used phospholipid. Among the engineering aspects of the process, a comparison between different membrane substances was performed. Efficiency increases with a higher phospholipid concentration but decreases with the addition of cholesterol. Due to the higher bending modulus, liposome formation is slowed down by cholesterol during liposome closure leading to a greater leakage of the model API. The encapsulation of bovine serum albumin and dextran, both investigated under different osmotic conditions, shows that an efflux negatively affects the encapsulation efficiency while an influx increases the stability. Overall, the process shows the potential for a very high encapsulation efficiency for macromolecules and future pharmaceutical applications.

scholarly journals Compatibility of Different Formulations in Pentravan® and Pentravan® Plus for Transdermal Drug Delivery

2021 ◽  
Vol 89 (4) ◽  
pp. 51
Author(s):  
Hudson Polonini ◽  
Sarah Taylor ◽  
Clark Zander
Keyword(s):  
Vitamin D3 ◽  
Transdermal Delivery ◽  
Scientific Community ◽  
Therapeutic Benefit ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Low Concentrations ◽  
The Stability ◽  
Potential Therapeutic Benefit ◽  
Metformin Hcl

The potential therapeutic benefit of transdermal delivery systems for some active pharmaceutical ingredients (APIs) has been well-established for decades within the scientific community. However, together with the clinical efficacy, there is the need for an evaluation of the stability of such APIs in bases with known transdermal capabilities, which is necessary to provide the compounding pharmacist with confidence when providing transdermal products. In this study, the stability of danazol, metformin HCl, and resveratrol as individual ingredients, as well as metformin HCl, resveratrol, and Vitamin D3 in combinations at bracketed high and low concentrations, were evaluated over a period of 6 months, using a ready-to-use transdermal vehicle for compounding pharmacies (Pentravan® or Pentravan® Plus). The five formulations tested (F1: Danazol 50 mg/g + MiodesinTM 85 mg/g in Pentravan®, F2: Metformin HCl 200 mg/g in Pentravan®, F3: Resveratrol 200 mg/g in Pentravan®, F4: Metformin HCl 100 mg/g + Resveratrol 100 mg/g + Vitamin D3 5000 IU in Pentravan®, and F5: Metformin HCl 200 mg/g + Resveratrol 200 mg/g + Vitamin D3 5000 IU in Pentravan® Plus) presented a beyond-use date of at least 6 months, presenting high convenience for the compounding pharmacies.

scholarly journals The effect of polymorphism on active pharmaceutical ingredients: A review

2020 ◽  
Vol 11 (2) ◽  
pp. 1621-1630
Author(s):  
Ahmad Ainurofiq ◽  
Kezia Esther Dinda ◽  
Maya Widia Pangestika ◽  
Ulia Himawati ◽  
Wening Dyah Wardhani ◽  
...  
Keyword(s):  
Production Process ◽  
Chemical Properties ◽  
Crystal Form ◽  
Pharmaceutical Products ◽  
Polymorphic Form ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
The Stability ◽  
Main Components ◽  
Crystalline Forms

Active pharmaceutical ingredients (API) are the main components in the production process of pharmaceutical products. If the API has a good quality, then it will lead to good pharmaceutical products. API consists of more than one different crystal form which, then forms a polymorph through the process of polymorphism. Until now, API polymorphism is still a big challenge in the pharmaceutical industry. That is because the nature of polymorphism is difficult to predict. One of them is by crystallizing molecules in one or many crystalline forms or combining with other molecules to form stable co-crystal. This process will lead to several polymorph forms of one certain API. Sometimes, these forms will have characteristics that differ one to another. Each polymorph has different mechanical, physical, thermal, and chemical properties that will affect the solubility, dissolution, bioavailability, stability, bioequivalence, and manufacturing of the API. Therefore to know the nature of an API, it is necessary to characterize the polymorphic form of the API before. If the form is not incompatible with the formulation, it can cause a failure in the production process. This review will discuss the effect of polymorphism on the physicochemical properties of API. It is hoped that this review can become the basis for improving the stability and effectiveness of pharmaceutical products.

Reversed-Phase High Performance Liquid Chromatographic Analysis of Three First Line Anti-Tuberculosis Drugs

2019 ◽  
Vol 69 (12) ◽  
pp. 3590-3592
Author(s):  
Nela Bibire ◽  
Romeo Iulian Olariu ◽  
Luminita Agoroaei ◽  
Madalina Vieriu ◽  
Alina Diana Panainte ◽  
...  
Keyword(s):  
High Performance ◽  
Biological Fluids ◽  
Gradient Elution ◽  
High Performance Liquid Chromatographic ◽  
Reversed Phase ◽  
Assay Method ◽  
Active Pharmaceutical Ingredients ◽  
First Line ◽  
Pharmaceutical Ingredients ◽  
Liquid Chromatographic

Active pharmaceutical ingredients such as isoniazid, pyrazinamide and rifampicin are among the most important first-line anti-tuberculosis drugs. A simple, rapid and sensitive reversed phase-high performance liquid chromatographic assay method for the simultaneous determination of isoniazid, pyrazinamide and rifampicin has been developed. Separation of the interest compounds was achieved in a 10 min chromatographic run in gradient elution mode on a Zorbax SB-C18 stainless steel column (150 � 4 mm, 5 mm) using a guard column containing the same stationary phase. The gradient elution was carried out with a mobile phase of 10% CH3CN aqueous solution for channel A and 50% CH3CN in pH = 6.8 phosphate buffer (20 mM), to which 1.5 mL triethylamine were added for channel B. Quantification of the analyzed substances was carried out spectrophotometrically at 269 nm. Detection limits of 0.48 mg/L for isoniazid, 0.52 mg/L for pyrazinamide and 0.48 mg/L for rifampicin were established for the developed assay method. The present work showed that the proposed analysis method was advantageous for simple and rapid analysis of the active pharmaceutical ingredients in pharmaceuticals and biological fluids.

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