Search or add a thesis

Advanced Search (Beta)
Home > Application of Various Strategies to Enhance the Solubility and Bioavailability of Rosuvastatin Calcium

Application of Various Strategies to Enhance the Solubility and Bioavailability of Rosuvastatin Calcium

Thesis Info

Access Option

External Link

Author

Sarfraz, Rai Muhammad

Program

PhD

Institute

The Islamia University of Bahawalpur

City

Bahawalpur

Province

Punjab

Country

Pakistan

Thesis Completing Year

2016

Thesis Completion Status

Completed

Subject

Applied Sciences

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/2797/1/Rai_Muhammad_Sarfraz_Pharmaceutics_2016_HSR_IU_Bahawalpur_25.08.2016.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725523112

Asian Research Index Whatsapp Chanel
Asian Research Index Whatsapp Chanel

Join our Whatsapp Channel to get regular updates.

Similar


The term ‘solubility’ is defined as an excess amount of solute that can be incorporated in a given amount of solvent. Solubility of poorly water-soluble drugs is one of the most emerging issue associated with these drugs to form a suitable dosage form that will provide desired pharmacological response. Their low solubility causes elimination of most of the drug from body as such, and desired therapeutic levels are not achieved. In recent years, a large number of drugs have been developed, but nearly 70% of new drugs have poor water solubility. Major part of the human body is made up of water. Therefore, drugs must be having a certain aqueous solubility. The solubility of drugs ultimately has strong impact on their bioavailability. Rosuvastatin calcium (RST) belongs to the Biopharmaceutics Classification System class II having low solubility and high permeability. It is a poorly water-soluble 3-hydroxy-3-methyl glutaryl CoA (HMG- CoA) reductase inhibitor. Efforts have been made to enhance solubility of these drugs. Different techniques have been used to enhance solubility of these poorly water soluble drugs such as reduction in particle size to increase surface area, thus increasing the dissolution rate of drug, solubilization in surfactant systems, formation of water-soluble complexes, drug derivatization such as strong electrolyte salt forms that usually have higher dissolution rate, producing liquisolid formulations, manipulation of the solid state of a drug substance to enhance drug dissolution i.e. by decreasing crystallinity of the drug substance through formation of solid solutions, solid dispersion formulations. Polymers are major players in these formulations to enhance solubility e.g., chitosan, polyvinyl pyrolidone, polyvinyl alcohol, β-cyclodextrin, etc. β-Cyclodextrin is one of the most efficient polymer among all of these to work as a carrier for these drugs to enhance solubility. In present work, fast disintegrating tablets (FDT’s) of rosuvastatin calcium were prepared by using β-cyclodextrin as polymer along with different super disintegrants such as kyron T 134 and sodium starch glycolate and microparticles were prepared by using β- cyclodextrin as polymer to enhance solubility. Microparticles were prepared by using solvent evaporation (solid dispersions), kneeding technique (inclusion complexes) and XXIfree radical polymerization to prepare hydrogel microparticles. Prepared formulations were evaluated by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Thermo Gravimetric Analysis (TGA), dissolution studies, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), zeta size and zeta potential, transmission electron microscopy (TEM), and stability studies to confirm enhancement in solubility. FDT’s were further characterized by wetting time, wetting volume, disintegration time, dispersion time etc. Different in vitro kinetic models such as zero order, first order, Higuchi, and Korsmeyer–Peppas were applied to determine the release behavior of drug from prepared formulations. Results were also statistically analyzed by mean, one-way analysis of variance (ANOVA), and p value was determined to check significant results. Results of FTIR and DSC of prepared formulations had revealed that stable complex was formed between drug and polymer. SEM study of formulations had shown that small openings were present on their surfaces. These openings facilitated the penetration of water and rapid release of drug. From PXRD study it was observed that drug had changed from crystalline to amorphous form. Internal morphology of TEM images had shown that drug was present inside of FDT’s and microparticles. Zeta size and zeta potential studies confirmed that microparticles had micron size and net charge was neutral. Wetting time, wetting volume, disintegration time, dispersion time, water absorption ratio of FDT’s were 43±1.15-96±1.5 seconds, 80±0.5-22±1.50 seconds, 3±1.50-77±1.50 seconds, 29±0.58-57±0.58 seconds and 1.10±0.01-2.00±0.02, respectively. FDT’s and microparticles dissolution studies had shown that FDT’s released 91- 97% (p=0.025) of drug while inclusion complexes and solid dispersions released 71-92% (p=0.15) of drug and hydrogel microparticles released upto 92% of drug (p=0.02). In contrast to prepared formulations, drug released from commercially available tablets of Rosuvastatin calcium was very less (43%). Due to acidic nature of Rosuvastatin calcium drug was more soluble at higher pH value i.e., at 6.8 as compared to 1.2 pH. Hydrogel microparticles containing Acrylamido-2-methyl propane sulphonic acid (AMPS) as monomer had shown pH independent swelling and shown better release than methacrylic acid (MAA) containing hydrogel microparticles. AMPS containing hydrogel microparticles released drug at both pH values but it was better at 6.8 than 1.2. Solubility studies revealed that prepared formulations had greater solubility at 6.8 pH phosphate buffer, 1.2 pH HCl buffer and in pure water than alone drug. All three types of formulations had enhanced solubility of Rosuvastatin calcium but it was highest at 6.8 pH phosphate buffer. FDT’s enhanced solubility of Rosuvastatin calcium 7.42 folds in HCl buffer of 1.2 pH, while in phosphate buffer of 6.8 pH 11.71 folds and in pure water 9.05 folds solubility was enhanced. Microparticles prepared by solvent evaporation had enhanced solubility 3.32 folds, 8.54 folds and 5.86 folds at 1.2 pH, 6.8 pH and in pure water, respectively. Hydrogel microparticles prepared by AMPS had enhanced solubility 7.53 folds, 10.66 folds and 7.30 folds at 1.2 pH, 6.8 pH and in pure water, respectively. In case of hydrogel microparticles containing MAA had no greater impact on solubility of Rosuvastatin calcium (RST) at 1.2 pH, while these enhanced solubility upto 9.59 folds and 6.9 folds at pH 6.8 and in pure water. From findings it was observed that solubility of Rosuvastatin calcium was enhanced by using these techniques. Pharmacokinetic data had also depicted that C max and AUC 0-24 were also greater for prepared formulations in contrast to RST commercially available tablets. Elimination half-life of drug was reduced upto 4 hours in our formulations. Toxicology data also shown that no toxic effects were observed from hematological, biochemical and histological studies. From findings of this study it was concluded that solubility of Rosuvastatin calcium was successfully enhanced by using techniques. Prepared formulations were found stable during stability studies of 6 month period. Thus, we can conclude that solubility of BCS class drugs can be enhanced by using these techniques with improved bioavailability.
Loading...
Loading...

Similar Books

Loading...

Similar Chapters

Loading...

Similar News

Loading...

Similar Articles

Loading...

Similar Article Headings

Loading...

Timeline of major events relating to the life of The Prophet(P)

Timeline of major events
relating to the life of The Prophet(P)

CE 570: Birth of the Prophet.
610: Beginning of the Revelation of The Qur’an.
613: The Prophet formally begins his Mission with preaching and advocacy.
615: Refuge of some Muslims in Abyssinia.
617: Siege of the Prophet and his family.
619: Death of the Prophet’s wife and his first-born son.
620: The Prophet’s Night Journey to Jerusalem and the Heavens.
620: Pledge of Aqabah in preparation for his migration.
622: Migration to Madeenah.
AH 02/CE 624: Battle of Badr.
03/625: Battle of Uhud.
05/627: Battle of the Trench.
06/628: Treaty of Hudaybia.
08/629: Makkah reverts to Islam.
08/630: Battle of Hunayn, Battle of Ta’ef.
09/631: Tabuk Expedition.
10/632: Farewell Pilgrimage.
11/632: The Prophet leaves this world.

* CE - Common Era. * AH - After Hijrah

امام جلال الدین السیوطی رحمہ اللہ کی زندگی اور علم تصوف میں خدمات

The Almighty Allah has sent many intellectual and pious people after the Last Prophet and Messenger Allah Subhan-o-Tala for the security of Den-e-Islam. They not noly Protect Deen-e-Islam from the foreign imovation but take their roles in its world over spreading. One among these prestigious personalities and intellectual is Jalal Ud Din Asoyothi (849-911). He was a multi sided personality. At the same time he was a great scholar, Author, Reviewer and genius intellectual among his friends. You are the author of approximately 700 books. He has touched my aspect of life in written works. While having such a busy and prestigious life of honesty, truthfulness, rejecting the materialistic life having a heart for the spiritual life. He started to leads the life of mysticism and till death did not leave the life of mystics persons. In this mystic’s life he has written and review many books. Due to this mysticism he was serves the humanity and protect Deen-e-Islam from the false beliefs. In this research paper some of the aspect of mysticism in the light of his research works has been discussed.

Purely Analytic Solutions to Some Multidimensional Viscous Flows With Heat Transfer

Exact solution of Navier-Stokes equations is possible only for very simple flow situations such as unidirectional flows. Due to the nonlinear nature of these equations their analytic solutions are rare and the situation gets worse in the case of unsteady and multidimensional flow problems. In this thesis we report highly accurate and purely analytic solutions to some steady/unsteady multidimensional viscous flows over flat surface. Heat transfer analysis has also been carried out where the flat surface is considered as a stretching sheet. In each case the skin friction and the rate of heat transfer has been reported. The issue of cooling of stretching sheet in the presence of viscous dissipation has been discussed in detail. We have considered multidimensional flows of viscous fluid over a flat plate in different flow situations such as flow over an impulsively started moving plate; flow over a stretching sheet, viscous flow in a channel of lower stretching wall, and the channel flow with lower wall as a stretching sheet in a rotating frame. In all the above mentioned flow situations similarity transformations have been used in order to normalize the problem. The reduced governing equations are then solved analytically. We have used homotopy analysis method to solve the governing nonlinear differential equa- tions. The results are purely analytic and highly accurate. The accuracy of results has been proved by calculating the residual errors and (or) giving the comparison with the existing re- sults. For unsteady flows it is worthy to mention here that our analytic solutions are uniformly valid for all time in the whole spatial domain.