Izhar Hussain

Survey of artemisinin production by diverse Artemisia species in northern Pakistan

BackgroundArtemisinin is the current drug of choice for treatment of malaria and a number of other diseases. It is obtained from the annual herb, Artemisia annua and some microbial sources by genetic engineering. There is a great concern that the artemisinin production at current rate will not meet the increasing demand by the pharmaceutical industry, so looking for additional sources is imperative.MethodsIn current study, artemisinin concentration was analysed and compared in the flowers, leaves, roots and stems of Artemisia annua and 14 other Artemisia species including two varieties each for Artemisia roxburghiana and Artemisia dracunculus using high performance liquid chromatography (HPLC).ResultsThe highest artemisinin concentration was detected in the leaves (0.44 ± 0.03%) and flowers (0.42 ± 0.03%) of A. annua, followed by the flowers (0.34 ± .02%) of A. bushriences and leaves (0.27 ± 0%) of A. dracunculus var dracunculus. The average concentration of artemisinin varied in the order of flowers > leaves > stems > roots.ConclusionThis study identifies twelve novel plant sources of artemisinin, which may be helpful for pharmaceutical production of artemisinin. This is the first report of quantitative comparison of artemisinin among a large number of Artemisia species.

Exploring the hydrogen-bond preference of N–H moieties in co-crystals assembled via O–H(acid)⋯N(py) intermolecular interactions

In order to establish the hydrogen-bond preference of an amide based N–H moiety faced with different CO or –OH hydrogen-bond acceptors, the crystal structures of several new co-crystals and salts were examined: 3-acetaminopyridine fumaric acid (2 : 1) 1, 4-(acetaminomethyl)pyridine fumaric acid (2 : 1) 2, 4-acetaminopyridine decanedioic (sebacic) acid (2 : 1) 3, 4-(acetaminomethyl)pyridine adipic acid (2 : 1) 4, 4-(acetaminomethyl)pyridine isophthalic acid (2 : 1) 5, 4-(acetaminomethyl)pyridinium 5-nitro-hydrogen isophthalate hydrate 6, 4-acetaminopyridinium hydrogenglutarate (1 : 1) 7. All co-crystals, 1–5, are constructed from an O–H(acid)⋯N(py) hydrogen bond and for the salts, 6–7, the primary synthon is the corresponding charge-assisted N–H+⋯−O interaction. The remaining N–H donor (on the amide moiety) shows a preference (4 out of 5) for the amide CO over the acid CO.

Ten years of co-crystal synthesis; the good, the bad, and the ugly

We present seven new co-crystals based around 1,4-diiodotetrafluorobenzene that illustrate some of the progress that has been made, as well as some of the challenges that remain, in the assembly of specific solid-state architectures using non-covalent interactions and relatively simple molecular building blocks.

Enlisting the scientifically unnoticed medicinal plants of Pakistan as a source of novel therapeutic agents showing anti-venom activity

Snake bite envenoming is a global occupational hazard and most of the people of the world trust in traditional medicine for snake poisoning. The present review elaborates scientifically un-investigated/ ignored medicinal plants of Pakistan showing chemical constituents of natural origin with possible mechanisms showing anti-venom activity. This review enlists 35 plants with their families, distribution in Pakistan, parts used traditionally for snake bite treatment and various active principles present in them. Compositae is the most excessive family, with 3 species, followed by Amaranthaceae, Apocynaceae, Asclepiadaceae, Caesalpinaceae, Labiatae, Pinaceae, Polygonaceae and Verbinaceae having 2 species of medicinal plants. While, one plant species belongs to each, Aizoaceae, Araceae, Boraginaceae, Chenopodiaceae, Cucurbitaceae, Euphorbiaceae, Flacourtiaceae, Gentianaceae, Malvaceae, Menispermaceae, Mimosaceae, Oxalidaceae, Papilionaceae, Plantaginaceae, Salvadoraceae and Solanaceae. As an antidote to snake poisoning, the traditional use of leaves (35%) is higher than roots (25%), whole plant (21%), flower (7%), wood (5%), fruit (5%) and milky juice (2%). Among life forms of plants, herbs (55%) are more excessively used as snake bite remedy than shrubs (31%) and trees (14%). This article may help the researchers to bring novelty in the field of natural products for the treatment of snake bite. However, chemical and pharmacological studies are necessary to confirm the anti-venom claims about these medicinal plants of Pakistan.

Effects of vegetative and flowering stages on the biosynthesis of artemisinin in Artemisia species.

Artemisinin is an endoperoxide sesquiterpene lactone, and has been proven to be very effective in treating drug resistant cases of malaria, cancer, etc. The compound is obtained from Artemisia species. In the current study, the effects of vegetative and flowering stages on artemisinin production were studied, to determine the proper harvesting time of naturally growing Artemisia species with the highest levels of artemisinin. Eight Artemisia species along with two varieties were selected for this analytical work. The results showed that artemisinin content was high in the leaves of Artemisia indica, A. sieversiana, A. roxburghiana var. roxburghiana, A. roxburghiana var. gratae, and A. parviflora at the flowering stage. The highest artemisinin content was measured in the leaves of A. dracunculus var. dracunculus. Upon comparisons of artemisinin content among the individual plant species, the highest amount of artemisinin was again in A. dracunculus var. dracunculus followed by A. sieversiana when harvested at the flowering stage. In overall comparisons, the plants at the flowering stage showed high levels of artemisinin, which is deemed the optimum harvesting time of Artemisia species in Pakistan for maximum artemisinin content.

The development of carbamazepine-succinic acid cocrystal tablet formulations with improved in vitro and in vivo performance

Abstract The use of soluble cocrystal for delivering drugs with low solubility, although a potentially effective approach, often suffers the problem of rapid disproportionation during dissolution, which negates the solubility advantages offered by the cocrystal. This necessitates their robust stabilization in order for successful use in a tablet dosage form. The cocrystal between carbamezepine and succinic acid (CBZ-SUC) exhibits a higher aqueous solubility than its dihydrate, which is the stable form of CBZ in water. Using this model system, we demonstrate an efficient and material-sparing tablet formulation screening approach enabled by intrinsic dissolution rate measurements. Three tablet formulations capable of stabilizing the cocrystal both under accelerated condition of 40 °C and 75% RH and during dissolution were developed using three different polymers, Soluplus® (F1), Kollidon VA/64 (F2) and Hydroxypropyl methyl cellulose acetate succinate (F3). When compared to a marketed product, Epitol® 200 mg tablets (F0), drug release after 60 min from formulations F1 (∼82%), F2 (∼95%) and F3 (∼95%) was all higher than that from Epitol® (79%) in a modified simulated intestinal fluid. Studies in albino rabbits show correspondingly better bioavailability of F1–F3 than Epitol.

Evaluation of Cefixime-Loaded Chitosan Microspheres: Analysis of Dissolution Data Using DDSolver

The objectives of this study were to fabricate cefixime-loaded chitosan microspheres with the ultimate goal of prolonging drug release and to analyze the influence of various process variables on the properties of microspheres such as mode of drug release. The cefixime-loaded chitosan microspheres were fabricated using a coacervation technique. Various process variables like volume of solvent for chitosan (glacial acetic acid), chitosan concentration, volume of phase separation agent (NaOH solution), and glutaraldehyde concentration were varied to fabricate nine different formulations. Dissolution data were evaluated using DDSolver, new software developed for the kinetic analysis of dissolution data. The microspheres were spherical, porous, and dark brown. They ranged in size from 253.13 ± 8.4 to 369.1 ± 13.7 µm, and the incorporation efficiency varied from 29.9 ± 32% to 49.3 ± 4.5%. The F5 formulation with a drug/polymer ratio of 1:3 (w/w) was the most suitable in terms of incorporation efficiency (49.3 ± 4.5%), flow characteristics (Hausner ratio = 1.4), and drug release properties. The drug release was sustained up to many hours. Fickian diffusion was the primary mode of drug release from all cefixime-loaded chitosan microsphere formulations. These results show that cefixime can be successfully microencapsulated into chitosan shells by coacervation, which is influenced significantly by formulation variables such as chitosan and glutaraldehyde concentration.

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

EVALUATION OF STUDENT’S PERCEPTION AND BEHAVIOR TOWARDS PLAGIARISM IN PAKISTANI UNIVERSITIES

The prevalence of academic delinquency in universities, predominantly in the form of plagiarism and cheating, is extensively conceded. Objectives: The objective of this study was to evaluate student’s perception and behavior towards plagiarism in Pakistani universities. Methods: This cross-sectional survey was conducted in 6 academic disciplines in 35 universities in Pakistan during 21.02.2011-21.04.2011. Expert interviewers and learned educationists carried out the interviews with the help of a structured questionnaire to evaluate student’s knowledge about plagiarism such as (i) student’s knowledge about HEC policy, (ii) student’s attitude towards plagiarism, (iii) student’s satisfaction towards plagiarism and cheating, and (iv) their views for penalties (What should be the penalties for 1st and 2nd occurrence of plagiarism?) and recorded the responses. Results: This survey was accomplished by 25742 students. The response rate for awareness about HEC policy about plagiarism showed that significantly (p<0.05) low percentage (94%) of students was unaware of this policy. The attitudes of significantly (p<0.05) high percentage of students towards plagiarism behavior were unacceptable. Significantly (p<0.05) high response rate towards attitudes regarding punishment for plagiarism was warning and report to HOD for first and second occurrence of this cheating, respectively. Conclusions: An extensive lack was found in the understanding of students towards plagiarism across all the universities. It is necessary to achieve balance between factors affecting plagiarism such avoidance, finding and sentence in case of detection.

Versatile Ligands for the Construction of Layered Metal-Containing Networks

The synthetic opportunities furnished by organic synthesis and the inherent structure-directing possibilities of coordination complexes have been combined in the assembly of a series of layered metal-containing hybrid materials. The supramolecular assembly relies on self-complementary non-covalent interactions, and in five of the six structures presented herein, N–H···O=C hydrogen bonds between acetamide moieties on neighbouring ligands provide the primary structure-direction tool as intended. The distances between metal ions are controlled by ligand···ligand hydrogen bonds and reside within a narrow and tuneable range. The following crystal structures are reported: [Cu(4-(3-pyridyl)-1-acetamidobenzene)2(1,1,1,5,5,5-hexafluoro-2,4-pentanedione)2] 1; [Cu(4-(acetamidomethyl)pyridine)2(1,1,1,5,5,5-hexafluoro-2,4-pentanedione)2]·2CH2Cl2 2; [Cu(3-acetamidopyridine)2(1,1,1,5,5,5-hexafluoro-2,4-pentanedione)2] 3; [Ni(3-acetamidopyridine)2(1,3-diphenyl-1,3-propanedione)2]·2CH2Cl2 4; [Ni(3-acetamidopyridine)2(1,3-diphenyl-1,3-propanedione)2] 5; and [Co(2-acetamidopyridine)2(1,3-diphenyl-1,3-propanedione)2]·2CH2Cl2 6.