scholarly journals Impact of Surface Properties of Core Material on the Stability of Hot Melt-Coated Multiparticulate Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 366
Author(s):  
Sonja Schertel ◽  
Sharareh Salar-Behzadi ◽  
Andreas Zimmer
Keyword(s):  
Crystal Growth ◽  
Surface Properties ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Product ◽  
Core Material ◽  
Metformin Hydrochloride ◽  
Hydrophobic Core ◽  
Formulation Development ◽  
Coating Composition ◽  
Hot Melt

Hot melt coating (HMC) of an active pharmaceutical ingredient (API) powder with lipid-based excipients is an innovative method for manufacturing patient-convenient dosage forms. However, drug release instability is still its main industrial challenge. The correlation between the unstable pharmaceutical product performance with the solid-state alteration of lipids is currently well-investigated. The remaining problem is the inconsistent release alteration of different APIs coated with the same lipid after storage, such as faster release in some cases and slower release in others. The interaction between API surface and lipid-based coating and its alteration during storage were investigated in this work. The surface properties of five different APIs and the coating composition of tripalmitin and polysorbate 65 were screened via Washburn and pendant drop methods, respectively. Metformin hydrochloride and hydrochlorothiazide particles were each coated with the coating composition. The water sorption alteration of coated particles and the crystal growth of tripalmitin in the coating after storage were measured via tensiometry and X-ray diffraction. The cleavage work necessary to overcome the adhesion of coating composition on the core surface was calculated for each API. The accelerated release of the polar core (metformin) after storage was correlated with a low cleavage work and a distinctive phase separation. In contrast, a decelerated release of the hydrophobic core (hydrochlorothiazide) was favored by the crystal growth of the lipid-based coating. The gained knowledge can be used to design the product stability during the formulation development.

scholarly journals Nanocrystalization: An Emerging Technology to Enhance the Bioavailability of Poorly Soluble Drugs

2019 ◽  
Vol 7 (4) ◽  
pp. 259-278 ◽  
Author(s):  
Kavita Joshi ◽  
Akhilesh Chandra ◽  
Keerti Jain ◽  
Sushama Talegaonkar
Keyword(s):  
Water Solubility ◽  
Drug Loading ◽  
Chemical Properties ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Product ◽  
Drug Formulation ◽  
Water Soluble ◽  
Drug Candidate ◽  
Formulation Development ◽  
New Formulation

Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.

scholarly journals CO-CRYSTALS: A REVIEW

2018 ◽  
Vol 8 (6-s) ◽  
pp. 350-358 ◽  
Author(s):  
Shilpa Chaudhari ◽  
Sarika Ankushrao Nikam ◽  
Neetu Khatri ◽  
Shubham Wakde
Keyword(s):  
Melting Point ◽  
Physicochemical Properties ◽  
Spray Drying ◽  
Supercritical Fluid ◽  
Oral Bioavailability ◽  
Aqueous Solubility ◽  
New Product ◽  
Active Pharmaceutical Ingredient ◽  
Pharmacological Properties ◽  
Hot Melt

In development of new product major constraints are poor aqueous solubility and low oral bioavailability. Crystallization is one the approach has been used for enhancement of solubility of poorly aqueous soluble drugs also helps to improve physicochemical properties such as melting point, tabletability, solubility, stability, bioavailability and permeability with preserving the pharmacological properties of the active pharmaceutical ingredient. Different methods have been used for the synthesis of cocrystal such as grinding, slurry, antisolvent, hot melt extrusion, sonocrystallization, supercritical fluid, spray drying etc. The article highlights the co-crystallization, its methods and significance.  

scholarly journals Vacuum Compression Molding as a Screening Tool to Investigate Carrier Suitability for Hot-Melt Extrusion Formulations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1019
Author(s):  
Gauri Shadambikar ◽  
Thomas Kipping ◽  
Nicole Di-Gallo ◽  
Alessandro-Giuseppe Elia ◽  
Anja-Nadine Knüttel ◽  
...  
Keyword(s):  
Screening Tool ◽  
Drug Carriers ◽  
Hot Melt Extrusion ◽  
Compression Molding ◽  
Simulated Gastric Fluid ◽  
Formulation Development ◽  
Melt Extrusion ◽  
Scanning Calorimetry ◽  
Production Scale ◽  
Hot Melt

Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck® MXP, Soluplus®, Kollidon® VA 64, Eudragit® EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations.

scholarly journals Preformulation Studies for Generic Omeprazole Magnesium Enteric Coated Tablets

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
C. O. Migoha ◽  
M. Ratansi ◽  
E. Kaale ◽  
G. Kagashe
Keyword(s):  
Visible Region ◽  
Active Pharmaceutical Ingredient ◽  
Test Time ◽  
Sieve Analysis ◽  
Formulation Development ◽  
Compressibility Index ◽  
Enteric Coated ◽  
Time Changes ◽  
Preformulation Studies ◽  
Tapped Density

Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API). Micromeritics properties: bulk density (BD) and tapped density (TD), compressibility index (Carr’s index), Hauser’s ratio (H), and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr’s index 17.5%, Hauser’s ratio 1.2, and sieve analysis time 5 minutes). There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350–2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.

scholarly journals An Updated Risk Assessment as Part of the QbD-Based Liposome Design and Development

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1071
Author(s):  
Zsófia Németh ◽  
Edina Pallagi ◽  
Dorina Gabriella Dobó ◽  
Gábor Kozma ◽  
Zoltán Kónya ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Active Pharmaceutical Ingredient ◽  
Experimental Models ◽  
Phospholipid Content ◽  
Formulation Development ◽  
Critical Material ◽  
Critical Material Attributes ◽  
Critical Process Parameters ◽  
Saline Solutions ◽  
Phosphate Buffered Saline

Liposomal formulation development is a challenging process. Certain factors have a critical influence on the characteristics of the liposomes, and even the relevant properties can vary based on the predefined interests of the research. In this paper, a Quality by Design-guided and Risk Assessment (RA)-based study was performed to determine the Critical Material Attributes and the Critical Process Parameters of an “intermediate” active pharmaceutical ingredient-free liposome formulation prepared via the thin-film hydration method, collect the Critical Quality Attributes of the future carrier system and show the process of narrowing a general initial RA for a specific case. The theoretical liposome design was proved through experimental models. The investigated critical factors covered the working temperature, the ratio between the wall-forming agents (phosphatidylcholine and cholesterol), the PEGylated phospholipid content (DPPE-PEG2000), the type of the hydration media (saline or phosphate-buffered saline solutions) and the cryoprotectants (glucose, sorbitol or trehalose). The characterisation results (size, surface charge, thermodynamic behaviours, formed structure and bonds) of the prepared liposomes supported the outcomes of the updated RA. The findings can be used as a basis for a particular study with specified circumstances.

scholarly journals Synthesis and physicochemical characterization of the impurities and the key intermediate of pemetrexed disodium, an anticancer drug

2016 ◽  
Author(s):  
Olga Michalak ◽  
Mariusz Gruza ◽  
Marta Łaszcz ◽  
Kinga Trzcińska ◽  
Anna Witkowska ◽  
...  
Keyword(s):  
Antineoplastic Agent ◽  
Physicochemical Characterization ◽  
Physicochemical Characteristic ◽  
Thermal Characteristics ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Product ◽  
Disodium Salt ◽  
Synthesis Methods ◽  
Pyrimidine Nucleotides ◽  
Pemetrexed Disodium

Pemetrexed is an antifolate antineoplastic agent that acts by inhibiting the formation of precursor purine and pyrimidine nucleotides. Pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal and cancer cells. A pharmaceutical product containing pemetrexed disodium as the active ingredient is used for the treatment of malignant pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). The European Medicine Agency and the U.S. Food and Drug Administration require complete physicochemical characteristic not only for an active pharmaceutical ingredient, but also for its key synthetic intermediates and the impurities formed during synthesis drug products. Therefore the development of the synthesis methods for impurities and new crystalline forms of pemetrexed diacid – a key intermediate of pemetrexed disodium was described. Physicochemical characterizations of impurities and pemetrexed diacid were performed by means of thermal analysis, spectroscopic methods and powder diffraction. Structures elucidation on the basis of two-dimensional NMR experiments were discussed in details. Additionally, in this work, the crystal structure of pemetreksed diacid form C will be presented, together with its spectroscopic and thermal characteristics. The identification of these impurities and the intermediate is essential for the quality control during the production of the pemetrexed disodium salt.

scholarly journals Solubility Enhancement of Diclofenac Using Solid Dispersions

2021 ◽  
Vol 5 (1) ◽  
pp. 1-6
Author(s):  
Mohd. Aamir Mirza ◽  
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Diclofenac Sodium ◽  
Active Pharmaceutical Ingredient ◽  
Solubility Enhancement ◽  
Solvent Evaporation ◽  
Limiting Factor ◽  
Formulation Development ◽  
Enhanced Solubility ◽  
Evaporation Technique

Background: The phenomenon which gives rise to a homogenous system, formed by the dissolution of solute in a solvent is known as solubility. Low solubility is the limiting factor in formulation development. Diclofenac being BCS class II drug have low aqueous solubility of 0.00401mg/ml. Amongst various solubility enhancement techniques, solid dispersion is the easiest one. Objective: Present work is primarily focused on the development of solid dispersions of diclofenac through solvent evaporation technique utilizing Eudragit E100 as a carrier. Methods: Solid dispersion consists of at least one active pharmaceutical ingredient as a carrier in solid state. Various methods for preparing solid dispersions includes melt extrusion, fusion lyophilization, spray drying, solvent evaporation, and super critical fluid (SCF) technology. Solvent evaporation technique is used among various solid dispersion methods. Conclusion: The enhanced solubility found to be 0.485mg/ml. The dissolution was performed using USP Type II apparatus was %CDR of pure drug and its solid dispersion in 8 hr were found out to be 45.14926% and 98.04758% respectively. Henceforth, solid dispersion technique results marked solubility enhancement of diclofenac sodium.

scholarly journals Spectroscopic Analysis of Melatonin in the Terahertz Frequency Range

Sensors ◽  
2018 ◽  
Vol 18 (12) ◽  
pp. 4098 ◽  
Author(s):  
Uroš Puc ◽  
Andreja Abina ◽  
Anton Jeglič ◽  
Aleksander Zidanšek ◽  
Irmantas Kašalynas ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Active Pharmaceutical Ingredient ◽  
Pharmaceutical Products ◽  
Pharmaceutical Product ◽  
Thz Spectroscopy ◽  
Terahertz Frequency ◽  
Thz Imaging ◽  
Pharmaceutical Ingredients ◽  
Indispensable Tool ◽  
First Time

There is a need for fast and reliable quality and authenticity control tools of pharmaceutical ingredients. Among others, hormone containing drugs and foods are subject to scrutiny. In this study, terahertz (THz) spectroscopy and THz imaging are applied for the first time to analyze melatonin and its pharmaceutical product Circadin. Melatonin is a hormone found naturally in the human body, which is responsible for the regulation of sleep-wake cycles. In the THz frequency region between 1.5 THz and 4.5 THz, characteristic melatonin spectral features at 3.21 THz, and a weaker one at 4.20 THz, are observed allowing for a quantitative analysis within the final products. Spectroscopic THz imaging of different concentrations of Circadin and melatonin as an active pharmaceutical ingredient in prepared pellets is also performed, which permits spatial recognition of these different substances. These results indicate that THz spectroscopy and imaging can be an indispensable tool, complementing Raman and Fourier transform infrared spectroscopies, in order to provide quality control of dietary supplements and other pharmaceutical products.

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