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 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.

US trade policy is putting at risk the sustainability of the generic/biosimilar industry and the drug supply chain

2021 ◽  
pp. 174113432199431
Author(s):  
María Fabiana Jorge
Keyword(s):  
Supply Chain ◽  
Trade Policy ◽  
Pharmaceutical Products ◽  
Drug Supply ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Us Trade Policy ◽  
Drug Supply Chain ◽  
Security Concern ◽  
The U.S

With the outbreak of the Coronavirus there is a new realization of the vulnerabilities of the U.S. drug supply chain. However, while such concerns may have been amplified by the pandemic, they preceded Covid-19 and were well documented before 2020. Indeed, in past years the U.S. Congress held several hearings addressing potential vulnerabilities in the U.S. drug supply chain, in part due to the increasing dependency on China as a dominant supplier of active pharmaceutical ingredients (APIs) and some finished pharmaceutical products. These vulnerabilities go well beyond health policy and constitute a national security concern. The article addresses how U.S. trade policy plays a significant role in shaping the pharmaceutical industry at home and abroad and is in part responsible for some of the current vulnerabilities of the U.S. drug supply chain.

scholarly journals Encapsulation of Active Pharmaceutical Ingredients in Lipid Micro/Nanoparticles for Oral Administration by Spray-Cooling

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1186
Author(s):  
Carmen S. Favaro-Trindade ◽  
Fernando E. de Matos Junior ◽  
Paula K. Okuro ◽  
João Dias-Ferreira ◽  
Amanda Cano ◽  
...  
Keyword(s):  
Oral Administration ◽  
Raw Materials ◽  
Low Cost ◽  
Pharmaceutical Formulations ◽  
Spray Cooling ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Taste And Odor ◽  
Cooling Technology ◽  
Simple Technology

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and many times to achieve a controlled release profile. It is a relatively simple technology, it does not require the use of low-cost solvents (mostly associated to toxicological risk), and it can be applied for lipid raw materials as excipients of oral pharmaceutical formulations. The objective of this work was to revise and discuss the advances of spray cooling technology, with a greater emphasis on the development of lipid micro/nanoparticles to the load of active pharmaceutical ingredients for oral administration.

Polymorphism control of active pharmaceutical ingredients

2021 ◽  
pp. 37-54
Author(s):  
Roman Petrovich Terekhov ◽  
Denis Igorevich Pankov ◽  
Ekaterina Aleksandrovna Anfinogenova ◽  
Irina Anatolievna Selivanova
Keyword(s):  
Active Pharmaceutical Ingredient ◽  
Development Stage ◽  
Poor Quality ◽  
Polymorphic Modification ◽  
High Tech ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Medicinal Substances ◽  
The Usa ◽  
Economic Union

Рolymorphism is receiving increasing attention due to its influence on the physicochemical and pharmacological properties of the active pharmaceutical ingredients (API) while maintaining the molecular structure. This review is devoted to the problem of APIs phase state control both at the development stage and during the circulation of the drug. The term «polymorphism» has different definitions depending on the branch of science. There is no unambiguous solution to this issue in the regulatory documentation of pharmaceutical industry either. Based on the analysis of literary sources, the article presents a comparison of pharmacopeia methods, recommended in Russian and foreign regulatory documents for the analysis of polymorphism of medicinal substances, including state pharmacopeias of Russia, Belarus, Kazakhstan, the USA, and Japan, as well as international pharmacopeias of the European Economic Union and the Eurasian Economic Union. The trend on using a complex of high-tech equipment is revealed. A systematic approach to analysis based on X-ray diffraction, thermal, spectral, microscopic, biological, and physical methods for determining constants makes it possible not only to identify the polymorphic modification of API, but also to characterize its structure, morphology, physicochemical properties and pharmacological activity. In the Russian Federation, the phenomenon of polymorphism is being studied especially intensively, and some control methods, such as biological methods, are validated only in Russian pharmacopeia. A promising direction for further research is the improvement and harmonization of regulatory documentation within the framework of this chemical and technological field of pharmacy. A global approach will help to reduce not only the probability of poor-quality products entering the market, but also the costs of establishing the authenticity of the active pharmaceutical ingredient produced.

Stability of extemporaneously prepared rosuvastatin oral suspension

2017 ◽  
Vol 74 (19) ◽  
pp. 1579-1583 ◽  
Author(s):  
Abdel Naser Zaid ◽  
Rania Shtayah ◽  
Ayman Qadumi ◽  
Mashour Ghanem ◽  
Rawan Qedan ◽  
...  
Keyword(s):  
Relative Humidity ◽  
High Performance ◽  
Room Temperature ◽  
Microbial Contamination ◽  
Active Pharmaceutical Ingredient ◽  
Storage Conditions ◽  
Dissolution Profile ◽  
Stability Studies ◽  
Organoleptic Properties ◽  
The Stability

Abstract Purpose The stability of an extemporaneously prepared rosuvastatin suspension stored over 30 days under various storage conditions was evaluated. Methods Rosuvastatin suspension was extemporaneously prepared using commercial rosuvastatin tablets as the source of active pharmaceutical ingredient. The organoleptic properties, dissolution profile, and stability of the formulation were investigated. For the stability studies, samples of the suspension were stored under 2 storage conditions, room temperature (25 °C and 60% relative humidity) and accelerated stability chambers (40 °C and 75% relative humidity). Viscosity, pH, organoleptic properties, and microbial contamination were evaluated according to the approved specifications. High-performance liquid chromatography was used for the analysis and quantification of rosuvastatin in selected samples. Microbiological investigations were also conducted. Results The prepared suspension showed acceptable organoleptic properties. It showed complete release of rosuvastatin within 15 minutes. The pH of the suspension was 9.8, which remained unchanged during the stability studies. The microbiological investigations demonstrated that the preparation was free of any microbial contamination. In addition, the suspension showed stability within at least the period of use of a 100-mL rosuvastatin bottle. Conclusion Extemporaneously prepared rosuvastatin 20-mg/mL suspension was stable for 30 days when stored at room temperature.

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 Quality Assessment of Antibiotic Oral Drug Formulations Marketed In Katsina State, Nigeria

1970 ◽  
Vol 7 (6) ◽  
pp. 6-10
Author(s):  
Mukhtar Gambo Lawal ◽  
Muhammad Dauda Mukhtar ◽  
Abdulkadir Magaji Magashi
Keyword(s):  
Active Ingredient ◽  
Active Pharmaceutical Ingredient ◽  
Oral Drug ◽  
Active Pharmaceutical Ingredients ◽  
Hplc Assay ◽  
Drug Formulations ◽  
Percentage Content ◽  
Pharmaceutical Ingredients ◽  
Three Samples ◽  
High Incidence

There are increasing reports on the high incidence of substandard drugs, especially in developing countries.Pharmaceutical products have been reported to contain either no, low, or excessive amounts of the active pharmaceutical ingredient (API). Inview of the above, 112 samples of six different antibiotic oral drug formulations were evaluated for chemical quality by assessing the presence and the percentage content of the stated active pharmaceutical ingredients using validated HPLC assay as described in the official monograph of the British and United Stated pharmacopoeia. The result indicates that 43 (38.4%) had active ingredients outside the set pharmacopoeial limit and therefore were non-compliant to the BP and the USP specifications for percentage content.  Ampiclox and Cotrimoxazole had the highest proportion of samples with active ingredient outside the pharmacopoeial limit, and in three samples (one Augmentin and two Ampiclox), no active ingredient was detected. The presence of API lower than the claimed content declared on the packaging was the primary cause of non-compliance. The potential implications of the use of substandard drugs are treatment failure and the development of drug-resistance.  

scholarly journals EVALUATION OF THE PRESENCE OF POLYMORPHIC FORMS AND INFLUENCE ON THE DISSOLUTION PROFILE OF TENOXICAM IN ACTIVE PHARMACEUTICAL INGREDIENT AND FORMULATIONS

2018 ◽  
Vol 2 (2) ◽  
pp. 27-36
Author(s):  
Aline Taís Fries ◽  
Natália Olegário ◽  
Sarah Chagas Campanharo ◽  
Vitor Paulo Pereira ◽  
Martin Steppe
Keyword(s):  
Chemical Properties ◽  
Pharmaceutical Formulations ◽  
Active Pharmaceutical Ingredient ◽  
Xrd Analysis ◽  
Pharmaceutical Products ◽  
In Vitro Dissolution ◽  
Dissolution Profile ◽  
Crystalline Structures ◽  
Polymorphic Forms

Polymorphism is a relatively common phenomenon among pharmaceutical compounds, and one of the main aspects to be considered in the production and development of medications. The investigation of polymorphism associated with oxicams, a group belonging to the class of non-steroidal anti-inflammatory drugs (NSAIDs) has increased in recent years and, in the case of tenoxicam, the existence of four polymorphic forms is reported in the literature. The objective of this study was to characterize the presence of different polymorphic forms of tenoxicam in active pharmaceutical ingredient and oral pharmaceutical formulations, as well as to evaluate the influence on in vitro dissolution. The characterization of the three samples of pharmaceutical ingredient of tenoxicam from different suppliers by X-Ray Diffraction (XRD), Infrared (IR) and dissolution profile indicated the presence of a form III crystalline structure, without presenting significant differences between the in vitro dissolution profiles analyzed, and a Dissolution Efficiency (DE%) of 60.30%, 60.70% and 72.34%, respectively. When the four pharmaceutical specialties of tenoxicam were submitted to XRD analysis, they also presented form III crystalline structures. Despite this, the formulations presented different dissolution profiles and a DE% of 75.23%, 83.69%, 78.19% and 90.63%, respectively, without compromising their quality. However, often polymorphism affects physico-chemical properties of drugs, showing the importance of studying this phenomenon, by correlating the presence of crystalline structures to alterations in the quality of active ingredients and pharmaceutical products.

scholarly journals Development of Analytical Profile of Lamotrigine and its API Formulation

2021 ◽  
pp. 111-114
Author(s):  
VISHAL CHAUDHARY ◽  
VASUNDHARA SAXENA
Keyword(s):  
Spectrophotometric Method ◽  
Quantitative Estimation ◽  
Pharmaceutical Formulations ◽  
Hplc Method ◽  
Active Pharmaceutical Ingredients ◽  
Pharmaceutical Ingredients ◽  
Rp Hplc ◽  
System Suitability ◽  
Bulk Drug

Objective: The objective of this review is to put a light on the development of lamotrigine and its active pharmaceutical ingredients formulation with proper demonstration. Method: In the present work, one of the most imperative spectrophotometric method which is RP-HPLC method has been developed for the quantitative estimation of lamotrigine in bulk and pharmaceutical formulations. UV spectrophotometric method which involves the determination of Lamotrigine in bulk and in bulk drug and pharmaceutical formulation has maximum absorption at 307.5nm in methanol. It obeys Beer’s and Lambert’s law in the concentration range of 5-45 µg/ml. A rapid and sensitive RP- HPLC Method with UV detection (270 nm) for routine analysis of Lamotrigine formulation was developed. Chromatography was performed with mobile phase containing a mixture of methanol and Phosphate buffer (65:35v/v) with flow rate 1.0 ml/min. In the range of 20-100 µg/ml, the linearity of lamotrigine shows a correlation co-efficient of 0.9998. The proposed method was validated by determining sensitivity and system suitability parameters.

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