Introduction
The Divine Promise to the human species at the time of its exit from the heavens – Q.02:38- 39 – was held through ages of human history. It started with Adam, continued through Enoch, Noah, Abraham, Isaac, Moses, Jesus and culminated with Muhammad. May Allah’s peace and blessings be upon them.
The foundations of Faith are, prima facie, based on the Absolute Supremacy of One Divine Being. The teachings of all Scriptures came from the same Divine Source with the purpose of providing guidance for a life of righteousness within societies along a Straight and Optimal Path
– Qur’an 06:126, 07:16; and The Torah/Proverbs 4:23-27.
The Qur’an is the grand finale of all Divine Revelations and the Ultimate Truth. Allah, The Exalted and The Almighty, guaranteed to preserve its Sacred Arabic Text in its entirety and original form safe from any satanic change – Q.15:09.
Enriched with themes, history, law, images, symbols, language, recitation and a unique literary style – it is a master piece of a revelation that has been bestowed on humanity as a matchless text signifying the very name it carries – Al Kitab – The Book.
As The Qur’an was being revealed on to the last of the Prophets - Prophet Muhammad, in the Arabic language, he would dictate it to his appointed companions to serve as scribes over the 23- year period of its phased-revelation.
The Qur’an contains the narratives of past nations and the events of future generations to facilitate comprehension of the meaning and value of the Qur’anic Message. It also sets out examples and analogies for people so that they may reflect and take heed - Q.39:27. Its message transcends...
The strongest and most crucial strategic and economic links in the south Asian region are the friendships between Pakistan and China. China and Pakistan assert that the people who live on either side of the Himalayas have interacted with one another in a trustworthy and sincere manner from ancient times. Chinese investment in the CPEC represents the greatest sum (62 billion dollars) ever between two friendly nations. China and Pakistan are dealing with numerous internal and external security challenges as a result of their strong friendship and significant investment in this project. Both nations, such as India and Afghanistan, are posing security problems to Pakistan, which has several security issues. The USA, India, the UK, and Israel are also causing strife and tension in Pakistan. These nations are also causing internal problems by sponsoring terrorist organizations like the Taliban and ISIS as well as nationalist organizations like the Baloch, the Lashkar-e-Jhangvi, and Sipah Muhammad. The challenges to Pakistan's internal security are discussed in this study.
Aim of present study was to development and evaluation of matrix patches of metoprolol tartrate containing enhancers for sustained and enhanced transdermal delivery. Ethyl cellulose (EC), poly vinyl pyrrolidone (PVP), eudragit RS 100 (ERS) and eudragit RL 100 (ERL) were used as film formers alone or in combination. Dibutyl phthalate was used as plasticizer. Patches were prepared by plate casting method. Polyvinyl alcohol was used to prepare backing membrane. Prepared polymeric matrix patches containing no enhancer were characterized for physical appearance, thickness, weight variation, moisture contents and moisture up take capacity. Fourier transform infrared (FTIR) spectroscopic studies of prepared patches were performed to identify any chemical and physical interaction between drug and excipients. In vitro drug release studies were carried out in phosphate buffer pH 7.4 by using paddle over disc method. Release mechanism was elucidated by subjecting the in vitro release data to kinetic analysis by using DDsolver ® excel based add in program. Scanning electron microscopy (SEM) was performed after release to further elaborate release process. In vitro permeation studies were performed on Franz diffusion cell by using excised rabbit skin. Three polymeric combinations i.e. EC-PVP, EC-ERL and ERS-ERL were selected for further incorporation of enhancers. Non-ionic surfactants i.e. Span 20, Span 60, Span 80, Span 85, Tween 20 and Tween 80 were incorporated in polymeric combination of EC and PVP as permeation enhancers in two concentrations of 5% and 10%. Combination of EC and ERL was used for preparation of matrix patches containing 10 % w/w of Isopropyl myristate (IPM), dimethyl sulphoxide (DMSO), span 20, tween 20 and eucalyptus oil as enhancers. Four different terpenes like eucalyptol, limonene, nerolidol and menthol were employed in polymeric combination of ERL and ERS, in concentrations of 5%, 10% and 15% w/w of polymer. Formulations were optimized after enhances addition. Patches after incorporation of enhancers were characterized for physical properties, FTIR and SEM analysis. In vitro release and permeation studies were carried out to compare effect of enhancers and their concentration on release. Selected patch formulations were subjected to in vivo studies by two periods, two treatments randomized, cross over design in rabbits (n =6) for pharmacokinetic comparison with oral solution administration. Skin irritation XXIstudies were performed on healthy volunteers for terpene containing patches by measuring level of erythema with Mexameter ® . In presence of non-ionic surfactants initial burst release of metoprolol from EC-PVP patches was increased. However, overall release was decreased due to improved physical appearance in presence of nonionic surfactants. Span 20 and Tween 20, which have saturated shorter fatty acid side chains, showed highest enhancement effect with 1.73 and 2.01 folds increase in permeation rate when compared to control, respectively. Incorporation of enhancers in patches of EC-ERL had not affected amount of drug release up to 24 hrs except that of formulation containing DMSO where fast release was observed. Highest permeation flux in EC-ERL patches was observed for formulation containing IPM with 2 fold enhancement in permeation. Permeation flux for patches was in order of control (with no enhancer) > IPM > Tween 20 > Span 20 > DMSO = eucalyptus oil. Results of in vitro permeation studies of patches containing terpenes showed that despite of decrease in drug release by incorporation of enhancers, there was increase in skin permeation of metoprolol. Release from patches was indirectly related to the lipophilicity of terpenes. Limonene was the most effective enhancer among the patches containing terpenes and enhancement effect of terpenes on metoprolol was in the rank order of limonene > menthol > nerolidol > eucalyptol. Enhancement effect was increased by increase in concentration of enhancer in all formulations. However, no direct linear relationship was observed between permeation rate and enhancer concentration. Pharmacokinetic analysis of in vivo data elucidated that application of Tween 20 containing transdermal patch increased systemic availability (1.13 fold) and prolonged half life (almost 10 times) of metoprolol tartrate in comparison to oral administration. Whereas no increase in metoprolol bioavailability was observed after IPM (10%) containing patch application but half life was increased 8 times when compared to oral administration. Limonene (15%) containing patch application exhibited 1.47 folds increase in bioavailability and t 1/2 was extended up to 16 times. Moreover, skin irritation studies in healthy volunteers revealed that metoprolol tartrate patches containing terpenes were well tolerated. XXIIIt can be concluded that tween 20, IPM and limonene can be successfully employed as efficient permeation enhancers for transdermal delivery of metoprolol tartrate from EC- PVP, EC-ERL and ERS-ERL matrix patches, respectively. Moreover, a single patch of metoprolol is capable to provide sustained continuous delivery of metoprolol for more than two days across skin. Thus application of metoprolol tartrate transdermal patches can be used as an alternative of oral route for the treatment of hypertension.