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Home > Photostabilization of Some Drugs by Liposomal Drug Delivery Systems

Photostabilization of Some Drugs by Liposomal Drug Delivery Systems

Thesis Info

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Author

Adeel Arsalan

Program

PhD

Institute

Baqai Medical University

City

Karachi

Province

Sindh

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Applied Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/8015/1/Adeel_Arsalan_Pharmaceutics_HSR_2017_BMU%2c%20Karachi_7.12.2017.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676726891301

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The present work involves a study of the photolysis of riboflavin (vitamin B2) (RF), norfloxacin (antibiotic) (NF) and cyanocobalamin (vitamin B12) (B12) in various liposomal preparations having a composition of cholesterol (CH) and phosphatidylcholine (PC) with a ratio of CH:PC (13.50: 10.80–16.20 mM) and the evaluation of the effect of compositional variations on the kinetics of degradation and photostabilization of these drugs. UV and visible spectroscopy, fluorimetry, dynamic light scattering (DLS), atomic force microscopy (AFM) and high performance liquid chromatography (HPLC) have been employed to investigate various aspects of this work. The literature on the analytical methods used in the study of liposomes, formulation of liposomes and stabilization of liposomal drugs has extensively been reviewed. The observations on the study of the individual drugs used are as follows. Riboflavin (RF) The apparent first–order rate constants (kobs) for the photolysis of RF in liposomal preparations lie in the range of 1.73–2.29×10–3 min–1 compared with a value of 8.08 × 10–3 min–1 for the photolysis of RF in aqueous solution (pH 7.4). The values of kobs decrease linearly with an increase in PC concentration in the range of 12.12–14.85 mM, indicating the stabilization effect of PC on RF with a stabilization ratio of around 4. This is confirmed by a loss of fluorescence intensity of RF with an increase in PC content as a result of the quenching of excited singlet state and the formation of a charge–transfer complex between PC and RF. The values of kobs decrease with an increase in PC concentration indicating the effect of PC on RF stabilization. The entrapment efficiency of RF in liposomes has been determined as 25.9–42.3%. The assay of RF and its photoproduct, lumichrome (LC), in liposomal preparations has been carried out by a two– ii component spectrometric assay at 445 and 356 nm with a correction for linear irrelevant absorption to eliminate interference from liposomal components. The study indicates that RF can be stabilized against light by a modification of the liposomal formulation with an increase in PC concentration. The mechanism of RF and PC interaction has been discussed. Norfloxacin (NF) The values of kobs for the photolysis of NF in liposomal preparations are in the range of 1.05–2.40×10–3 min–1 and depend on the concentration of PC in liposomes. The value of kobs for the photolysis of NF in aqueous solution (pH 7.4) is 8.13×10–3 min–1 indicating a stabilization ratio of 3–7 in various liposomal preparations. A linear relation between kobs and PC concentration with a negative slope has been observed to show that PC exerts a stabilizing effect on NF in liposomes. DLS has indicated an increase in the size of NF encapsulated liposomes with an increase in PC concentration. Similar to RF the quenching of excited singlet state of NF by PC indicated by a loss of fluorescence suggests an interaction between NF and PC to form a charge–transfer complex. It results in the reduction of NF to form [NF–] species which cause stabilization of NF in liposomal preparations. The entrapment efficiency of NF in liposomal preparations amounts to 41–56%. The mode of interaction of NF and PC is similar to that of RF and PC to cause stabilization of NF in liposomal preparations. Cyanocobalamin (B12) B12 is a relatively large molecule compared to RF and NF and its photochemical behavior in liposomes has also been studied. The values of kobs for the photolysis of B12 in liposomes have been found to be in the range 0.52–2.24 ×10–3 min–1, compared to that of 3.21×10–3 min–1 for B12 in aqueous solution (pH 5.0) and an entrapment efficiency in the range of 26.4–38.8%. In this case also a linear relation has been observed between the values of kobs and PC concentration with iii a negative slope indicating the influence of PC in inhibiting the rate of photolysis of B12. This also appears to be due to the involvement of a charge–transfer complex between B12 and PC that results in the stabilization of vitamin B12. The stabilization ratio of B12 in liposomal preparations has been determined as 1–6. The present study on the photolysis of RF, NF and B12 suggests that these drugs may be stabilized in liposomal preparations. The mode of stabilization involves the participation of a charge–transfer complex to cause the reduction of the drug to the species that have low susceptibility to photolysis. The values of the second–order rate constants for the photochemical interaction of RF, B12 and NF with PC are 1.48, 0.32 and 8.92×10–2 M–1 min–1, respectively, suggesting that PC exerts the greatest effect on the stabilization of RF, followed by those of B12 and NF. This could be due to the relative ease of electron donation from PC to the drug and charge–transfer complex formation between them. This would probably depend on the redox potentials of these drugs under the reaction conditions involved. On the basis of the results obtained in this study it may be suggested that such an approach could be useful in the stabilization of photoliable drugs in liposomal preparations.
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اہل بیت اطہار کے حضور

اہلِ بیت اطہارؓ کے حضور

دیں کو ملی جِلا ہے درِ اہلِ بیت سے
زندہ ہوئی وفا ہے درِ اہلِ بیت سے

قسمت کا در کھلا ہے درِ اہلِ بیت سے
سب کچھ مجھے ملا ہے درِ اہلِ بیت سے

مشکل میں جب گیا ہوں درِ اہل بیت پر
مشکل ہوئی کشا ہے درِ اہلِ بیت سے

ہر غم کا ہے علاج درِ اہلِ بیت ہی
ملتی ہر اک شفا ہے درِ اہلِ بیت سے

ہر چیز مل گئی ہے درِ اہلِ بیت سے
ہر کام ہو گیا ہے درِ اہلِ بیت سے

کرتا نہیں سوال کسی اور در پہ یہ
تائب تو مانگتا ہے درِ اہلِ بیت سے

The Influence of Theory of Planned Behavior and Technology Acceptance Models on Behavioral Intentions in Online Grocery Shopping in Pekanbaru City

This study was carried out to investigate the impact of integrating two theories on consumer behavior, namely the Theory of Planned Behavior (TPB) and Technology Acceptance Models (TAM), on the consumer behavior intention in online food shopping in the city of Pekanbaru. A descriptive quantitative method was employed in this research, utilizing purposive sampling techniques. The study involved 174 female respondents aged 18 and above, residing in the city of Pekanbaru, who had previously engaged in online food shopping. The analysis of data was performed utilizing the Structural Equation Modeling-Partial Least Squares (SEM-PLS) approach. The results indicated that both the perceived usefulness (PU) and perceived ease of use have a notable impact on attitude (ATT). Furthermore, behavioral intention was significantly influenced by attitude (ATT), subjective norm (SN), and perceived behavioral control (PBC). The originality of this study resides in combining the Theory of Planned Behavior (TPB) and Technology Acceptance Models (TAM) within the specific context of online food shopping in the city of Pekanbaru. This study is expected to contribute to the field of consumer behavior, especially the behavior of consumers in Pekanbaru regarding online food shopping.

Role of Financial and Operating Leverage in Firms? Profitability During Pre & Post 2008 Financial Crisis: An Investigation from Chemical Sector of Pakistan

This study investigates the role of financial and operating leverages in firms? profitability before and after financial recession/crisis of 2008 focusing on chemical sector firms listed on the Pakistan Stock Exchange (PSX). The period of study selected is from 2004 to 2015. The ROE is taken as dependent variable. The Financial Leverage (FL) and Operating Leverage (OL) are chosen as independent variables or predictors. Three other variables like Assets Utilization (AU), Non-Debt Tax Shield (NDTS) and Age have been introduced as control variables. Another variable named Pre/Post is introduced as a dummy variable for the indication of pre and post financial crisis 2008. A population of all 43 firms listed on PSX is selected. The 29 chosen firms relate to the chemical sector directly whereas 14 firms are indirectly related to the chemical industry.The data used in the analysis has been gathered from secondary sources i.e. from the SBP?s publications. The regression model used is panel linear model (PLM). The unbalanced data panel has been used in the analysis. Similarly, the random effect approach has been applied.The Stata statistical software has been used to estimate the relationship between predicted/dependent and predictor/independent variables. Following outcomes have been accomplished after the examination; the FL has a negative but significant relationship with the firm?s profitability whereas the OL has a positive but non-significant relationship with the firm?s profitability. The AU has shown a positive and significant relationship with the firm?s profitability. Whereas other predictors like Age, NTDS have proved a positive but non-significant relationship with the firm?s ?ROE?. Both types of leverages have shown a negative impact on the firm?s profitability after the global financial crisis in 2008. Keywords: Profitability, Financial leverage, Operating leverage, Assets Utilization, Age, non-debt tax shield, Financial Recession/Crisis 2008 and Pre/Post.