scholarly journals A Systematic Approach in the Development of the Morphologically-Directed Raman Spectroscopy Methodology for Characterizing Nasal Suspension Drug Products

2021 ◽  
Vol 23 (4) ◽  
Author(s):  
Gonçalo Farias ◽  
Jagdeep Shur ◽  
Robert Price ◽  
Elizabeth Bielski ◽  
Bryan Newman
Keyword(s):  
Particle Size ◽  
Raman Spectroscopy ◽  
Dissolution Rate ◽  
Systematic Approach ◽  
Active Pharmaceutical Ingredient ◽  
Drug Products ◽  
Complex Formulation ◽  
Automated Imaging ◽  
Plume Geometry ◽  
Analytical Tools

AbstractDemonstrating bioequivalence (BE) of nasal suspension sprays is a challenging task. Analytical tools are required to determine the particle size of the active pharmaceutical ingredient (API) and the structure of a relatively complex formulation. This study investigated the utility of the morphologically-directed Raman spectroscopy (MDRS) method to investigate the particle size distribution (PSD) of nasal suspensions. Dissolution was also investigated as an orthogonal technique. Nasal suspension formulations containing different PSD of mometasone furoate monohydrate (MFM) were manufactured. The PSD of the MFM batches was characterized before formulation manufacture using laser diffraction and automated imaging. Upon formulation manufacture, the droplet size, single actuation content, spray pattern, plume geometry, the API dissolution rate, and the API PSD by MDRS were determined. A systematic approach was utilized to develop a robust method for the analysis of the PSD of MFM in Nasonex® and four test formulations containing the MFM API with different particle size specifications. Although the PSD between distinct techniques cannot be directly compared due to inherent differences between these methodologies, the same trend is observed for three out of the four batches. Dissolution analysis confirmed the trend observed by MDRS in terms of PSD. For suspension-based nasal products, MDRS allows the measurement of API PSD which is critical for BE assessment. This approach has been approved for use in lieu of a comparative clinical endpoint BE study [1]. The correlation observed between PSD and dissolution rate extends the use of dissolution as a critical analytical tool demonstrating BE between test and reference products.

Submicron Simultaneous IR and Raman Spectroscopy (IR+Raman): Breakthrough Developments in Optical Photothermal IR (O-PTIR) Combined for Enhanced Failure Analysis

2019 ◽  
Author(s):  
Jay Anderson ◽  
Mustafa Kansiz ◽  
Michael Lo ◽  
Curtis Marcott
Keyword(s):  
Raman Spectroscopy ◽  
Failure Analysis ◽  
Data Quality ◽  
Raman Spectra ◽  
Spatial Resolution ◽  
Far Field ◽  
Field Mode ◽  
Microscopic Scale ◽  
Analytical Tools ◽  
Ir And Raman

Abstract Failure analysis of organics at the microscopic scale is an increasingly important requirement, with traditional analytical tools such as FTIR and Raman microscopy, having significant limitations in either spatial resolution or data quality. We introduce here a new method of obtaining Infrared microspectroscopic information, at the submicron level in reflection (far-field) mode, called Optical-Photothermal Infrared (O-PTIR) spectroscopy, that can also generate simultaneous Raman spectra, from the same spot, at the same time and with the same spatial resolution. This novel combination of these two correlative techniques can be considered to be complimentary and confirmatory, in which the IR confirms the Raman result and vice-versa, to yield more accurate and therefore more confident organic unknowns analysis.

Formulation and Evaluation of Nanosuspension of Simvastatin

2015 ◽  
Vol 8 (2) ◽  
pp. 2858-2873
Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid
Keyword(s):  
Particle Size ◽  
Zeta Potential ◽  
Factorial Design ◽  
Dissolution Rate ◽  
In Vitro Dissolution ◽  
Total Drug ◽  
23 Factorial Design ◽  
Rate Of Dissolution

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.

Azithromycin nanosuspension preparation using evaporative precipitation into aqueous solution (EPAS) method and its comparative dissolution study

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohammad Hossain Shariare ◽  
Tonmoy Kumar Mondal ◽  
Hani Alothaid ◽  
Md. Didaruzzaman Sohel ◽  
MD Wadud ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Particle Size ◽  
Dissolution Rate ◽  
Average Particle Size ◽  
Scale Up ◽  
Average Particle ◽  
Total Drug ◽  
Residual Solvent ◽  
Dissolution Study ◽  
Drug Content

Aim: EPAS (evaporative precipitation into aqueous solution) was used in the current studies to prepare azithromycin nanosuspensions and investigate the physicochemical characteristics for the nanosuspension batches with the aim of enhancing the dissolution rate of the nanopreparation to improve bioavailability. Methods: EPAS method used in this study for preparing azithromycin nanosuspension was achieved through developing an in-house instrumentation method. Particle size distribution was measured using Zetasizer Nano S without sample dilution. Dissolved azithromycin nanosuspensions were also compared with raw azithromycin powder and commercially available products. Total drug content of nanosuspension batches were measured using an Ultra-Performance Liquid Chromatography (UPLC) system with Photodiode Array (PDA) detector while residual solvent was measured using gas chromatography (GC). Results: The average particle size of azithromycin nanosuspension was 447.2 nm and total drug content was measured to be 97.81% upon recovery. Dissolution study data showed significant increase in dissolution rate for nanosuspension batch when compared to raw azithromycin and commercial version (microsuspension). The residual solvent found for azithromycin nanosuspension is 0.000098023 mg/ mL or 98.023 ppb. Conclusion: EPAS was successfully used to prepare azithromycin nanoparticles that exhibited significantly enhanced dissolution rate. Further studies are required to scale up the process and determine long term stability of the nanoparticles.

scholarly journals Particle size dependency of dissolution rate and human bioavailability of phenytoin in powders and phenytoin-polyethylene glycol solid dispersions.

1984 ◽  
Vol 32 (10) ◽  
pp. 4130-4136 ◽  
Author(s):  
SHIGERU YAKOU ◽  
KUMIKO UMEHARA ◽  
TAKASHI SONOBE ◽  
TSUNEJI NAGAI ◽  
MASAYASU SUGIHARA ◽  
...  
Keyword(s):  
Particle Size ◽  
Polyethylene Glycol ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Size Dependency

Liquid antisolvent recrystallization and solid dispersion of flufenamic acid with polyvinylpyrrolidone K-30

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Rahul Kumar ◽  
Sanjay Kumar ◽  
Pranava Chaudhari ◽  
Amit K. Thakur
Keyword(s):  
Particle Size ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Fine Particles ◽  
Xrd Analysis ◽  
Solution Concentration ◽  
Injection Rate ◽  
Size Reduction ◽  
Flufenamic Acid ◽  
Particle Size Reduction

Abstract Flufenamic acid (FFA) is a Biopharmaceutical Classification System- II (BCS-II) class drug with poor bioavailability and a lower dissolution rate. Particle size reduction is one of the conventional approaches to increase the dissolution rate and subsequently the bioavailability. The use of the liquid antisolvent method for particle size reduction of FFA was studied in this work. Ethanol and water were used as solvent and antisolvent, respectively. Experimental parameters such as solution concentration (10–40 mg/ml), flow rate (120–480 ml/h), temperature (298–328 K) and stirring speed (200–800 rpm) were investigated. Furthermore, the solid dispersion of FFA was prepared with polyvinylpyrrolidone K-30 (PVP K-30) with different weight ratios (1:1, 1:2, 1:3 and 1:4) and samples were characterized using SEM, FTIR and XRD techniques. The experimental investigation revealed that higher values of concentration, injection rate, stirring speed, along with lower temperature favored the formation of fine particles. SEM analysis revealed that the morphology of raw FFA changed from rock-like to rectangular-like after liquid antisolvent recrystallization. FTIR analysis validated the presence of hydrogen bonding between FFA and PVP in solid dispersion. XRD analysis showed no significant change in the crystallinity of the processed FFA.

scholarly journals Automated System for Kinetic Analysis of Particle Size Distributions for Pharmaceutically Relevant Systems

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
John-Bruce D. Green ◽  
Phillip W. Carter ◽  
Yingqing Zhang ◽  
Dipa Patel ◽  
Priyanka Kotha ◽  
...  
Keyword(s):  
Particle Size ◽  
Clinical Importance ◽  
Automated System ◽  
Size Distributions ◽  
Mixing Conditions ◽  
Particle Size Distributions ◽  
Complex Formulation ◽  
Wide Range ◽  
Key Variables ◽  
Kinetics Of

Detailing the kinetics of particle formation for pharmaceutically relevant solutions is challenging, especially when considering the combination of formulations, containers, and timescales of clinical importance. This paper describes a method for using commercial software Automate with a stream-selector valve capable of sampling container solutions from within an environmental chamber. The tool was built to monitor changes in particle size distributions via instrumental particle counters but can be adapted to other solution-based sensors. The tool and methodology were demonstrated to be highly effective for measuring dynamic changes in emulsion globule distributions as a function of storage and mixing conditions important for parenteral nutrition. Higher levels of agitation induced the fastest growth of large globules (≥5 μm) while the gentler conditions actually showed a decrease in the number of these large globules. The same methodology recorded calcium phosphate precipitation kinetics as a function of [Ca2+] and pH. This automated system is readily adaptable to a wide range of pharmaceutically relevant systems where the particle size is expected to vary with time. This instrumentation can dramatically reduce the time and resources needed to probe complex formulation issues while providing new insights for monitoring the kinetics as a function of key variables.

scholarly journals Comparative Analysis of the QbD Approach in the Pharmaceutical Industry

2019 ◽  
Vol 8 (4) ◽  
pp. 20-26 ◽  
Author(s):  
S. A. Rozhnova ◽  
A. V. Tsypkina
Keyword(s):  
Comparative Analysis ◽  
Drug Development ◽  
Systematic Approach ◽  
New Drugs ◽  
Pharmaceutical Development ◽  
Drug Products ◽  
New Drug ◽  
Eurasian Economic Union ◽  
Pharmaceutical Manufacturers ◽  
Economic Union

Introduction. In the development and introduction of medicines into production, the aim of pharmaceutical manufacturers is to comply with the principle of «Quality-by-Design» (QbD). The International Council for Harmonisation (ICH) has created a number of GxP standards, which have become the regulatory framework for the development of documentation regulating the requirements for the development and production of drug products for countries focused on bringing their products to the world pharmaceutical market. The analysis of the system of regulation of pharmaceutical stages of development of new drugs in the territory of the Eurasian Economic Union was not considered, but for the formation of a systematic approach to the management of the process of pharmaceutical development it is necessary to describe them.Aim. To analyze the possibility of applying the QbD principle to the process of drug development at domestic pharmaceutical enterprises.Materials and methods. Content analysis of scientific publications, system and comparative analysis, sociological methods of research in the field of pharmaceutical development.Results and discussions. Regulatory state requirements to the organization and conduct of drug development procedures are analyzed and described. A number of systemic and sectoral problems typical for domestic pharmaceutical manufacturers in the organization of the development and implementation of new drug products. It is established that one of the main problems for Russian enterprises was the organization of the process as a whole and its individual procedures. To solve the problem of organization of procedures for the development and implementation of new medicines, we formed a methodological support, developed on the basis of a systematic approach and international requirements from the quality system.Conclusion. The main problem identified by the manufacturers is the lack of methodological support for the organization of the processes of pharmaceutical development and the introduction of new drugs in the part of research going to the stage of preclinical and clinical development. The decisions adopted by the Eurasian Economic Union do not affect such aspects of pharmaceutical development regulation as the organization of processes, their management and methodological support aimed at the implementation of the QbD principle. To solve this problem, we have developed guidelines for the implementation of the processes of pharmaceutical development and the introduction of new drug products, which allowed us to apply unified and formalized approaches to their organization. 

Review on Pharmaceutical Co-Crystals and Design Strategies

2021 ◽  
pp. 175-180
Author(s):  
A.V.S. Ksheera Bhavani ◽  
A. Lakshmi Usha ◽  
Kayala Ashritha ◽  
Radha Rani E.
Keyword(s):  
Aqueous Solubility ◽  
Active Pharmaceutical Ingredient ◽  
Crystal Formation ◽  
Stoichiometric Ratio ◽  
Design Strategies ◽  
Great Opportunity ◽  
Drug Products ◽  
Drug Substances ◽  
Component Systems ◽  
Physical And Chemical

Poor aqueous solubility and low oral bioavailability of an active pharmaceutical ingredient are the major constraints during the development of new product. Various approaches have been used for enhancement of solubility of poorly aqueous soluble drugs, but success of these approaches depends on physical and chemical nature of the molecules being developed. Co-crystallization of drug substances offers a great opportunity for the development of new drug products with superior physicochemical such as melting point, tabletability, solubility, stability, bioavailability and permeability, while preserving the pharmacological properties of the active pharmaceutical ingredient. Co-crystals are multi component systems in which two components, an active pharmaceutical ingredient and a coformer are present in stoichiometric ratio and bonded together with non-covalent interactions in the crystal lattice. This review article presents a systematic overview of pharmaceutical co-crystals, differences between co-crystals with salts, solvates and hydrates are summarized along with the advantages of co-crystals with examples. The theoretical parameters underlying the selection of coformers and screening of co-crystals have been summarized and different methods of co-crystal formation and evaluation have been explained.

scholarly journals DEVELOPMENT OF RITONAVIR LOADED NANOPARTICLES: IN VITRO AND IN VIVO CHARACTERIZATION

2018 ◽  
Vol 11 (3) ◽  
pp. 284
Author(s):  
Pravin S Patil ◽  
Shashikant C Dhawale
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Dissolution Rate ◽  
Drug Carrier ◽  
Entrapment Efficiency ◽  
Significant Rise ◽  
Scanning Calorimetry ◽  
In Vitro Drug Release

 Objective: The purpose of the present investigation was to develop a nanosuspension to improve dissolution rate and oral bioavailability of ritonavir.Methods: Extended-release ritonavir loaded nanoparticles were prepared using the polymeric system by nanoprecipitation technique. Further, the effect of Eudragit RL100 (polymeric matrix) and polyvinyl alcohol (surfactant) was investigated on particle size and distribution, drug content, entrapment efficiency, and in vitro drug release from nanosuspension where a strong influence of polymeric contents was observed. Drug-excipient compatibility and amorphous nature of drug in prepared nanoparticles were confirmed by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies, respectively.Results: Hydrophobic portions of Eudragit RL100 could result in enhanced encapsulation efficiency. However, increase in polymer and surfactant contents lead to enlarged particle size proportionately as confirmed by transmission electron microscopy. Nanosuspension showed a significant rise in dissolution rate with complete in vitro drug release as well as higher bioavailability in rats compared to the pure drug.Conclusion: The nanoprecipitation technique used in present research could be further explored for the development of different antiretroviral drug carrier therapeutics.

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