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Studies of the Formulation and Evaluation of Controlled Release Matrix Tablets With Selected Anti-Diabetic Drugs

Thesis Info

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Author

Khan, Saifullah

Program

PhD

Institute

Gomal University

City

Dera Ismail Khan

Province

KPK

Country

Pakistan

Thesis Completing Year

2017

Thesis Completion Status

Completed

Subject

Pharmaceutics

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/13179/1/Saif%20Phd%20Thesis%2030.08.16.f%20%2830-10-17%29%20final.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727269121

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Acarbose, an oral a-glycosidase inhibitor, is frequently employed for management of Non-Insulin dependent diabetes. Primarily it deeds by reducing plasma glucose level through slothful absorption of starches and sugars from intestine.Glipizide & Repaglinide, are 2nd generation sulfonyl-urea and act, by increasing insulin secretion, but binds to different betacell receptor sites. They are used alone / adjunct to diet to the management of type-II (non-insulin dependent) diabetes mellitus in patients whose hyper-glycemia cannot be controlled by diet and exercise alone.Owing to their short half life, dosage frequency / schedule, patient non-compliance, economic factors and adverse effects on GIT, they are wellthought-out to be good candidates for preparation into Modified release, dosage forms. Keeping this in view during pre-formulation work, emphasis was laid on detailed study of parameters such as optical-rotation, melting-point, %age-purity, particle-size, sizedistribution, solubility at different temperatures & pH, FTIR spectra for conformation, λ max determination, micro-meritic properties of selected drug(s), polymers and in-active ingredients used in this research work. DSC and FTiR studies were done to check interaction of drug with polymers and excipients.During this study attention was also concentrated on some contributing approaches to improve the dissolution rates of Glipizide & Repaglinide, which are insoluble/sparingly soluble drug(s). For this purpose solid dispersions of Glipizide & Repaglinide, were prepared by solvent evaporation technique, using Carbopole,, as dispersion carrier. The drug carrier interactions were studied through SEM, DSC, FTIR & X-ray diffraction analysis. The influence of proportional amount of the carrier on the dissolution rate of Glipizide & Repaglinide, were also investigated. The results did not show any chemical decomposition or well defined interaction between drugs and carrier, indicating a praiseworthy compatibility amid them. The solid dispersions with Carbopole, demonstrated an evident increase in the dissolution rate and solubility of Glipizide & Repaglinide. The boost in the dissolution rate and solubility of Glipizide & Repaglinide, could be attributed to several factors such as improved wettability, local solubilization, conversion from crystalline form to amorphous form and drugs particle size reduction. Directly compressed CR matrix tablets, using granular Ethocel® standard premium & Ethocel® standard F P premium were aimed, equipped and assessed invitro, in the first instance, followed by invivo evaluation of the best Dept. of Pharmaceutics, Faculty of Pharmacy, Gomal University, D.I.Khan, K.P. products. Physico chemical evaluation of the framed tablets was accomplished, using different physico.chemical, dimensional and QC-tests etc. Findings of all these experiments were found to be with in acceptable range and tablets met the pharmacotechnical requirments. The influence of different viscosity grades of Ethocel® on t h e t ab l et characteristics, drug release rates, release-patterns & release-kinetics were probed. Ethocel® with lower viscosity grades revealed good compressibility, resultant in harder tablets. Particle size and amount of polymer used were found to be the determining factors, in regulating the release rates of Acarbose, Glipizide & Repaglinide, from the tablets. The mechanism of drug release from the tablets seemed to differ from formulation to formulation, principally dependent on the amount of Ethocel® and particle size of the polymer used. More over the research concentrated on the consequence of partial replacement of primary active/ in-active ingredients (lactose) by various coexcipients such as HPMC, starch & CMC on the release rate and mechanism of drugs release from the matrix tablets. All of the coexcipients used improved the release.rates to different extent.Invitro studies revealed that tablet formulations containing polymer Ehocel® standard 7FP-premium, at D: P ratio 010: 3 & 01:3 were the best amidst the preparations for all three drugs (Acarbose, Glipizide & Repaglinide) singly, as they delivered boosted release patterns with optimum amount of the drugs released in 024 hrs, and due to their extended release rates, with either zero or near to zero-order release kinetics.The optimized Acarbose, Glipizide & Repaglinide matrix tablets designs were further used for invitro & invivo bio-availability, bio-equivalence & stabilities studies as compared to the comparative studies with available marketed, conventional tablets of Acarbose, Glipizide & Repaglinide. Stability studies were accomplished on the optimized preparation for a period of 1 year both in ambient and accelerated conditions and the tablets were re-assessed physicochemicaly at different intervals of time. The results attained demonstrated maximum stability for 1 year.The comparative invitro dissolution studies, revealed prolonged release rate of test formulations as 96.39%, 88.09% & 89.73% of Acarbose, Glipizide & Repaglinide released after 24 hours, correspondingly, while in all of the available marketed conventional formulations, drugs were released well before 24 hours. Invivo studies of the best formulated tablets were led by using HPLC based modified techniques meant at analysis of Acarbose, Glipizide & Repaglinide in rabbit’s-plasma. Measured plasma concentrations of the drug(s) were used in calculation of pharmaco-kinetic parameters for the CR, test tablets and reference marketed conventional preparations of Acarbose ,Glipizide & Repaglinide using PK Win Dept. of Pharmaceutics, Faculty of Pharmacy, Gomal University, D.I.Khan, K.P. Nolin, software(Win.Nolin®Ver 5.2.1 (Pharsight Corporation, Mountan.View, CA, USA). Intentionally prolonged Tmax, t1/2 and MRT0-t of the test CR matrix tablets of model drug(s) point toward smooth and extended absorption phase of the drugs under research. The test CR, tablets exhibited better and linear in-vitro & in-vivo correlation as compared to reference marketed, conventional tablet preparations. Conclusion: It is concluded that a good controlled release formulation of Acarbose, Glipizide and Repaglinide can be prepared without risk of possible interactions using Ethocel® standard 7FP and Ethocel® 7 Premium polymer to avoid risk of side effects of Acarbose, Glipizide & Repaglinide and to improve patient compliance. Hence it is determined that acarbose,Glipizide & Repaglinide can be loaded to controlled release matrix tablet for the treatment of diabetes mellitus with better compliance and improve efficacy.
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آرزوؔ لکھنوی

آرزوؔ لکھنوی
جناب آرزوؔ جلال لکھنوی کے جانشین اور اردو زبان و ادب کے ماہر و محقق تھے اس پر ان کی نگاہ بڑی وسیع تھی، انہوں نے اردو شاعری میں زبان کی سادگی و سہولت یا موجودہ اصطلاح میں ہندوستانیت کا نیا نمونہ قائم کیا، وہ حتی الامکان عربی اور فارسی کے مشکل الفاظ اور ترکیبوں سے پرہیز اور خالص ہندوستانی الفاظ استعمال کرتے تھے، جن شعراء نے ان کی تقلید کی کوشش کی وہ کامیاب نہ ہوسکے اور ان کی شاعری یا ہندی کوتاہ بن گئی یا بے رنگ و بے مزہ ہوگئی، آرزو کی یہ خصوصیت تھی کہ انہوں نے زبان کی ہندوستانیت کے ساتھ اردو شاعری کا آب ورنگ اور اس کی دلآویزی قائم رکھی، جو زبان پر ان کی غیر معمولی قدرت کا ثبوت ہے، انہوں نے اپنے کلام کے کئی مجموعے فغانِ آرزو، جہان آرزو، اور سریلی بانسری یادگار چھوڑے ہیں، ان دونوں اساتذہ کے بعد لکھنو پرانی یادگار سے خالی ہوگیا، بلکہ ان پر اس دورہی کا خاتمہ ہوگیا ، اﷲ تعالیٰ ان کی مغفرت فرمائے۔
(شاہ معین الدین ندوی، مئی ۱۹۵۱ء)

 

اسلامی اخلاقیات واقدار کے فروغ میں خاندانی ماحول کا کردار؛معاصرانہ چیلنجز اور لائحہ عمل The role of family environment in the development of Islamic ethics and values, Contemporary challenges, and action plan

Islamic rules and moral values are unique in all aspects. The members of Muslim Ummah have always tried to promote them. At the national level, this duty was carried out by people at different levels whether they were teachers, businessmen or lay man of the society. At international level, some rulers, business professionals and religious leaders played their role. Man's first relationship is with family. This relationship is the cornerstone in the development of a personality.  There has been a lot of change taken place in the family system. In the past, due to the limited necessities of life the financial responsibility was limited to a few people. Media was not that advanced and bold and family members were loving and respectful. With the beginning of advance era, human needs were widened and to satisfy them, women started participating in economic activities along with men. Due to which the child was shifted from his home to day care centre, while the media gave birth to the social media, the stories of compassion and care in home became the past. In the present era, there is a dire need to remove these barriers that hinder the development of Islamic values through balance between income and expenditure, positive and moderate use of media and positive attitude in family. These issues will be discussed under the answers to the following questions. What is the role of family in the development of Islamic ethics? What are the problems faced by the family in the development of Islamic moral values? What are the solutions to the present-day problems?  

The Role of Organizational Justice and Culture in Relationships Between Leadership Styles and Employees’ Performance

The present study aimed to examine the impact of leadership styles (transformational & transactional) of the head of departments on employees (teachers) performance working in the academic department of higher educational institutions in Khyber Pakhtunkhwa, Pakistan. In similar vein, current study also examined mediating role of organizational justice and culture in relationship between leadership styles and teachers’ performance. For this purpose, data was collected from the both teachers and head of departments in the selected HEIs. The same data was then analyzed by using different statistical tools like correlation, regression, mediation and test of significance. In this regard, correlation analysis shows that all research variables are significantly correlated (table 4.14), wherein, correlation between transformational style and employees performance is (R=.915 & P-value=.000), transactional style (R=.816 & P-value=.000), organizational justice (R=.815 & P-value =.000) and organizational culture (R=.849 & P-value =.000). Similarly, cause-n-effect relationship shows that there is significant impact of predictors on criterion variable (table 4.15), wherein, the results showed that the transformational leadership is stronger predictor of employees’ performance (p- .000) as compared to transactional leadership (.020). Likewise, the mediation results (four models, table 4.40) shows that mediating variables (organizational justice & culture) partially mediate the relationship between the predictors and the criterion (tables 4.16 to 4.30a). In same line, test of significance shows diverse results about mean differences among demographic groups of respondents (tables 4.32 to 4.39). The results show that out of fourteen (14) hypotheses, eleven (11) were accepted and three (3) were rejected. However, findings of current study were positioned in Chapter 5, where these findings (current study) were compared with existing research (previous research) findings. In light of this positioning, conclusion were drawn based on certain recommendations and implications. Keywords: The Leadership Styles, Organizational Justice, Organizational Culture, Employees Performance & Higher Education Institutions