Macromolecular Prodrugs of Aspirin with HPMC: A Nano Particulate Drug Design, Characterization, and Pharmacokinetic Studies

Muhammad Ajaz Hussain,Khawar Abbas,Muhammad Sher,Muhammad Nawaz Tahir,Wolfgang Tremel,Mohammad Saeed Iqbal,Muhammad Amin,Munair Badshah 한국고분자학회 2011 Macromolecular Research Vol.19 No.12

This article presents the synthesis of novel hydroxypropylmethylcellulose (HPMC)-aspirin (ASP) conjugates,i.e. macromolecular prodrugs, through the reaction of HPMC with ASP after its in situ activation by 4-methylbenzenesulfonyl chloride. The highly pure ASP prodrugs obtained by this homogeneous and elegant esterification method were characterized using different spectroscopic and chromatographic techniques. Nanoparticulate drug design was successfully achieved by the conversion of free hydroxyls of the polymer into acetates. Transmission electron microscopy and scanning electron microscopy showed nanoparticle formation with the major population size distribution of around 450 nm. Nevertheless, the pharmacokinetics of the HPMC conjugates were studied using high performance liquid chromatography. The pharmacokinetic data indicated that a single dose of 132.6 mg of HPMC-ASP was well tolerated in animal studies without any adverse effects. The maximum plasma concentration (C_max) of HPMC-ASP was found to be 14.6 μg·L^-1 with a t_max of 1 h. The plasma half-life and clearance and the volume of HPMC-ASP distribution were 4.6 h, 3.23 L·h^-1, and 21.8 L·kg^-1, respectively. The elimination of HPMC-ASP followed first-order kinetics with r^2 of 0.9643. The results presented in this paper show the great potential of HPMCASP as a more effective, safe, and stable prodrug.

Physicochemical Characterization of Artemether Solid Dispersions with Hydrophilic Carriers by Freeze Dried and Melt Methods

Muhammad Tayyab Ansari,Shahid Karim,Nazar Muhammad Ranjha,Nisar Hussain Shah,Sher Muhammad 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.6

Solid dispersions of artemether (ARM), a poorly soluble drug, were prepared using polyvinylpyrrolidone (PVPK25, MW 25000) and polyethyleneglycol (PEG4000, MW 4000) as excipients. These dispersions were studied by physical mixture, freeze-drying, and melting methods. They were characterized by X-ray diffraction pattern, fourier transform infrared spectrophotometry, differential scanning calorimetery, and dissolution studies. X-ray diffraction pattern revealed the complete crystalline nature of artemether, whereas physical mixtures, melt mixtures (MM), and freeze-dried solid dispersions (FDSD) of ARM-PVP and ARM-PEG showed reduced peak intensities with increased PVP/PEG content. PEG showed lower decreases in intensity than PVP preparations. Differential scanning calorimetery also confirmed this finding by showing either a small or absent endotherm. Red shifts in O-H stretching vibrations of ARM were higher in the MM of ARM-PVP than its FDSD as exhibited by fourier transform infrared spectrophotometry. The carbonyl peak of PEG was blue shifted in MM and FDSD, whereas the C=O peak of PVP was red shifted in FDSD and MM, indicating different H-bonding by PEG and PVP with ARM. The rate of dissolution (phosphate buffer at pH 4.5) was improved up to 4-fold in MM and FDSD compared to artemether, and up to 50% compared to physical mixtures. The preparation of solid dispersions influenced the rate of dissolution at various drug-carrier ratios, i.e., the dissolution order of 1:1-1:4 ratio was MM > FDSD; FDSD > MM at 1:6-1:8 ratios of both ARM-PVP and ARM-PEG; and FDSD of ARM-PEG > FDSD of ARM-PVP > MM of ARM-PEG > MM of ARM-PVP at a 1:10 ratio.

Butyrylcholinesterase Inhibitory Guaianolides from Amberboa ramosa

Sher Bahadar Khan,Azhar-ul-Haq,Shagufta Perveen,Nighat Afza,Abdul Malik,Sarfraz Ahmad Nawaz,Muhammad Raza Shah,Muhammad Iqbal Choudhary 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.2

Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as 8α-hydroxy-11β−methyl-1αH, 5αH, 6βH, 7αH, 11αH-guai-10(14), 4(15)-dien-6, 12-olide(1), 3β, 8α-dihydroxy-11α−methyl-1αH, 5αH, 6βH, 7αH, 11βH-guai-10(14), 4 (15)-dien-6, 12-olide (2), 3β, 4α, 8α-trihydroxy-4β-(hydroxymethyl)- 1αH, 5αH, 6βH, 7αH-guai-10(14), 11(13)-dien-6, 12-olide (3), 3β, 4α, 8α-trihydroxy-4β- (chloromethyl)-1αH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6, 12-olide(4), 3β, 4α, dihydroxy- 4β-(hydroxymethyl)-1αH, 5αH, 6βH, 7αH-guai-10(14),11(13)-dien-6, 12-olide(5), 3β, 4α-dihydroxy- 4β- (chloromethyl)-8α-(4-hydroxymethacrylate)-1αH, 5αH, 6βH, 7αH-guai-10(14),11 (13)-dien-6,12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.

Variability and Predictability of Summer Monsoon Rainfall over Pakistan

Adnan Muhammad,Khan Firdos,Rehman Nadia,Ali Shaukat,Hassan Sher Shah,Dogar Muhammad Mubashar,Mehmood Shahbaz,Hasson Shabehul 한국기상학회 2021 Asia-Pacific Journal of Atmospheric Sciences Vol.57 No.1

Rainfall variability associated with the South Asian Summer Monsoon has increased in recent decades, particularly at the northwestern monsoon margins over Pakistan, leading to more frequent and intense hydro-meteorological extremes that have adversely affected the agrarian economy, water and food security in the country. Devising effective strategies to ensure sustainable development in Pakistan thus requires that the monsoonal rainfall be predicted on an inter-annual scale. Here, we predicted the inter- and intra-annual variability of the monsoonal rainfall over Pakistan and its possible drivers using a linear statistical forecast model of the principal component (PC) regression analysis. For this purpose, highly correlated PCs of the National Centre for Environmental Prediction (NCEP) based sea level pressure, horizontal and meridional winds to the observed rainfall for the period 2001–2013 were ingested in a stepwise multiple regression model, which was further validated for the duration of 2014–2015. Our results suggest that featuring correlation coefficient, mean absolute error, mean bias, and root mean square error of 0.75, 42.23, −14.92 and 60.65, respectively, the model exhibits robust skill in predicting the inter-annual monsoonal rainfall variability at its extreme northwestern margins over Pakistan.

Butyrylcholinesterase Inhibitory Guaianolides from Amberboa ramosa

Khan Sher Bahadar,Haq Azhar-ul,Perveen Shagufta,Afza Nighat,Malik Abdul,Nawaz Sarfraz Ahmad,Shah Muhammad Raza,Choudhary Muhammad lqbal The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.2

Phytochemical investigation of the whole plant of Amberboa ramosa led to the isolation of six sesquiterpene lactones which could be identified as $8{\alpha}$-hydroxy-$11{\beta}$-methyl-$1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H,\;11{\alpha}H-guai-10(14)$, 4(15)-dien-6, 12-olide(2), $3{\beta},\;8{\alpha}-dihydroxy-11{\alpha}-methyl-1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H,\;11{\beta}H-guai-10(14)$, 4(15)-dien-6, 12-olide (2), $3{\beta},\;4{\alpha},\;8{\alpha}-trihydroxy-4{\beta}(hydroxymethyl)-1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H-guai-10(14)$, 11(13)-dien-6, 12-olide (3), $3{\beta},\;4{\alpha},\;8{\alpha}-trihydroxy-4{\beta}-(chloromethyl)-1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H-guai-10(14)$, 11(13)-dien-6, 12-olide(4), $3{\beta},\;4{\alpha},\;dihydroxy-4{\beta}-(hydroxymethyl)-1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H-guai-10(14)$, 11(13)-dien-6, 12-olide(5), $3{\beta},\;4{\alpha}-dihydroxy-4{\beta}-(chloromethyl)-8{\alpha}-(4-hydroxymethacrylate)-1{\alpha}H,\;5{\alpha}H,\;6{\beta}H,\;7{\alpha}H-guai-10(14)$, 11(13)-dien-6, 12-olide (6) by spectroscopic methods. All of them showed inhibitory potential against butyrylcholinesterase.

Supplemental potassium mediates antioxidant metabolism, physiological processes, and osmoregulation to confer salt stress tolerance in cabbage (Brassica oleracea L.)

Waqas Ahmad,Chaudhary Muhammad Ayyub,Muhammad Asif Shehzad,Khurram Ziaf,Muhammad Ijaz,Ahmad Sher,Tahira Abbas,Jamil Shafi 한국원예학회 2019 Horticulture, Environment, and Biotechnology Vol.60 No.6

Soil salinity is one of the severe threats of climate change that inflicts heavy losses to vegetable production. Potassium (K) has been considered essential approach against abiotic stresses in food crops, however, understanding of K regulated mechanisms for inducing tolerance to NaCl stress in cabbage (Brassica oleracea L.) plants is, still elusive. Here, we report the supplemental K effects on antioxidant defense system and physiological processes that may influence the cabbage production under saline conditions. Initially, cabbage varieties (‘Stone Head’, ‘Golden Acre’, ‘9j-940’, ‘Beauty Ball’, ‘Green Ball’, ‘Green Rise’, ‘Marco F-1’) were tested under NaCl stress (50, 100, 150, and 200 mM) for their higher growth, vigor index and mineral contents. The identified cabbage var. salt-tolerant, cv. Beauty Ball (BB) and salt-sensitive cv. Green Ball (GB) were further exposed to foliar K (5 and 10 mM solutions of KNO3) under the same NaCl regimes. NaCl stress markedly inhibited photosynthetic efficiency, water status and chlorophyll pigments, thereby, resulted in reduced dry biomass of both varieties. Nevertheless, exogenous K spray at 10 mM caused positive gain in leaf water relations, chlorophyll contents in both cabbage varieties. The ameliorative impacts of K were more pronounced in salt-tolerant cv. BB as compared to salt-sensitive cv. GB in terms of higher accumulation of total soluble proteins, total free amino acids, proline contents, upregulated antioxidant activities and enhanced gas exchange characteristics. Hence, improvement in growth and K+/Na+ ratio of cabbage plants by foliar K application (10 mM) were related to up-regulation of physiological and biochemical mechanisms under saline conditions.

Assessment of antibacterial cellulose nanocomposites for water permeability and salt rejection

Sher Bahadar Khan,Khalid A. Alamry,Elham N. Bifari,Abdullah M. Asiri,Muhammad Yasir,Lassaad Gzara,Rehan Zulfiqar Ahmad 한국공업화학회 2015 Journal of Industrial and Engineering Chemistry Vol.24 No.-

Anti-bacterial nanocomposites (NC1–NC4) based on cellulose acetate were prepared by dispersing ZnO nanofillers in the cellulose acetate matrix. Anti-bacterial nanocomposites were structurally and morphological examined by XRD (X-ray powder diffraction), FESEM (field emission scanning electron microscopy), and FT-IR (Fourier transform infrared) spectroscopy. All the spectroscopic techniques suggested that nanocomposites are successfully synthesized. All the nanocomposites showed antibacterial activity which increased as a function of zinc oxide. Further the selectivity of anti-bacterial nanocomposites was investigated toward different metal ions, including Zn2+, Cd2+, Pb2+, Mn2+, Ni2+, Fe2+, Al3+, Sb3+, and Sr3+. The selectivity data suggests that nanocomposites are more selective toward Fe2+. NC1 displayed highest uptake aptitude for Fe2+ with highest distribution coefficient of 7549.123 mL g1. Therefore, NC1 was subjected to water permeability to explore the role of antibacterial nanocomposite as membrane for water purification. The results suggest that these materials are possibly appropriate for water treatments.

The U.S. war crimes in Afghanistan

Dost Muhammad Barrech,Mir Sher Baz Khetran 아시아사회과학학회 2022 Jornal of Asia Social Science Vol.7 No.3

The incident of 9/11, by and large, brought great changes in international politics. The US-led War on Terror (WOT) against the culprits involved in the 9/11 incidents caused irreparable damage to Afghanistan. Surprisingly, none of the perpetrators involved in 9/11 belonged to Afghanistan nor did the attacker Al-Qaeda have any genesis with the people of Afghanistan. The price Afghanistan paid in WOT is unimaginable that can never be compensated. Over the last two decades, the US-led war witnessed colossal war crimes of the people of Afghanistan. The country saw growing war crimes committed by the U.S. forces in the shape of the killing of innocent civilians, women rapes, abductions of innocent people, massacring of masses by drone strikes. The invasion of Afghanistan according to many experts was a geo-strategic move of the US in a bid to accelerate its presence in the region and to counter growing Chinese and Russian influence, keeping closed eyes on Pakistan nuclear assets. Having squandered twenty years, the US neither eliminated terrorism nor Taliban. Instead, Washington inked Doha agreement with the hardcore Taliban who are unfit and inexperienced to rule the country are expected to be espousing the U.S. trajectory in committing further war crimes. This paper, thus, will examine the US war crimes in war-torn Afghanistan in the last two decades.

Pakistan-Central Asia Connectivity: Role of Railways

Mir Sher Baz Khetran,Mian Ahmad N. Salik,Mahrukh Khan,Muhammad Taimur Khan 아시아사회과학학회 2021 Jornal of Asia Social Science Vol.5 No.2

Prosperity and progress require shared inter regional and intra-regional collaboration, utilizing resources at their maximum and exploring new avenues for transit and trade. Being part of a landlocked but resource-rich region, Central Asian states require improved access to regional markets including Pakistan, China, India and the countries of West Asia. And countries like Pakistan also need to boost trade with Central Asia. As a result of this possible mutual collaboration and economic benefits, railways can constitute a strategic opportunity for Turkmenistan, Uzbekistan, Kyrgyzstan, Kazakhstan and Tajikistan to transport their goods and market them more competitively on the regional and global market, while also benefiting other countries through CPEC. Uzbekistan s Deputy Prime Minister Elyor Ganiev paid a two day visit to Pakistan on 27th of May and met with Prime Minister Imran Khan and briefed him on the transport railway corridor Uzbekistan-Mazar-i-Sharif-Kabul-Peshawar. Uzbekistan shared with Pakistan its plan for an international railway route connecting the two countries via Afghanistan.

Ternary composites of SnO₂ with RGO and PEDOT:PSS for high lithium storage ability

Selim Arif Sher Shah,Shoaib Muhammad,Won-Sub Yoon,유필진 한국고분자학회 2015 한국고분자학회 학술대회 연구논문 초록집 Vol.2015 No.10