Muhammad Sohail Arshad

Diclofenac residues as the cause of vulture population decline in Pakistan.

The Oriental white-backed vulture (OWBV; Gyps bengalensis) was once one of the most common raptors in the Indian subcontinent. A population decline of >95%, starting in the 1990s, was first noted at Keoladeo National Park, India. Since then, catastrophic declines, also involving Gyps indicus and Gyps tenuirostris, have continued to be reported across the subcontinent. Consequently these vultures are now listed as critically endangered by BirdLife International. In 2000, the Peregrine Fund initiated its Asian Vulture Crisis Project with the Ornithological Society of Pakistan, establishing study sites at 16 OWBV colonies in the Kasur, Khanewal and Muzaffargarh–Layyah Districts of Pakistan to measure mortality at over 2,400 active nest sites. Between 2000 and 2003, high annual adult and subadult mortality (5–86%) and resulting population declines (34–95%) (ref. 5 and M.G., manuscript in preparation) were associated with renal failure and visceral gout. Here, we provide results that directly correlate residues of the anti-inflammatory drug diclofenac with renal failure. Diclofenac residues and renal disease were reproduced experimentally in OWBVs by direct oral exposure and through feeding vultures diclofenac-treated livestock. We propose that residues of veterinary diclofenac are responsible for the OWBV decline.

Development of solid dispersions of artemisinin for transdermal delivery

Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin.

Porous Inorganic Drug Delivery Systems—a Review

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Improvement of solubility, dissolution and stability profile of artemether solid dispersions and self emulsified solid dispersions by solvent evaporation method

Abstract The purpose of this study was to investigate changes in the water solubility of artemether; a poorly soluble drug used for the treatment of malaria. Different solid dispersions (SDs) of artemether were prepared using artemether and polyethylene glycol 6000 at ratio 12:88 (Group 1), self-emulsified solid dispersions (SESDs) containing artemether, polyethylene glycol 6000, cremophor-A-25, olive oil, hydroxypropylmethylcellulose and transcutol in the ratio 12:75:5:4:2:2, respectively (Group 2). SESDs were also prepared by substituting cremophor-A-25 in Group 2 with poloxamer 188 (noted as Group 3). Each of these preparations was formulated using physical mixing and the solvent evaporation method. Aqueous solubility of artemether improved 11-, 95- and 102-fold, while dissolution (in simulated gastric fluid) increased 3-, 13- and 14-fold, for formulation groups 1, 2 and 3, respectively. X-ray diffraction patterns of SDs indicated a decrease in peak intensities at 10° implying reduced artemether crystallinity. Scanning electron micrographs invariably revealed embedment of artemether by various excipients and a glassy appearance for solvent evaporated mixtures for all three formulation Groups. Our findings indicate improved hydrophilic interactions for drug particles yield greater solubility and dissolution in the following order for artemether formulating methods: solvent evaporation mixtures > physical mixtures > pure artemether.

Recurrent spontaneous splenic rupture in a patient with congenital factor XIII deficiency.

We describe an unusual presentation of factor XIII (FXIII) deficiency in a 17-year-old boy who was diagnosed with this congenital deficiency at the age of 18 months. He had a history of spontaneous splenic rupture 8 years ago, which was managed conservatively. He now presented with sudden severe abdominal and left shoulder pain for 1 day, with no history of antecedent trauma. He was in shock, and examination revealed diffuse peritonitis. A computed tomography scan showed a grade IV splenic laceration. He was taken as an emergency to the operating room where he was found to have a shattered spleen, and a splenectomy was performed. He received cryoprecipitate transfusions perioperatively. After an uneventful recovery, the patient was discharged. To the best of our knowledge, this is the first described case of a recurrent splenic rupture in a patient with FXIII deficiency.

Development of an ANN optimized mucoadhesive buccal tablet containing flurbiprofen and lidocaine for dental pain

Abstract A novel mucoadhesive buccal tablet containing flurbiprofen (FLB) and lidocaine HCl (LID) was prepared to relieve dental pain. Tablet formulations (F1-F9) were prepared using variable quantities of mucoadhesive agents, hydroxypropyl methyl cellulose (HPMC) and sodium alginate (SA). The formulations were evaluated for their physicochemical properties, mucoadhesive strength and mucoadhesion time, swellability index and in vitro release of active agents. Release of both drugs depended on the relative ratio of HPMC:SA. However, mucoadhesive strength and mucoadhesion time were better in formulations, containing higher proportions of HPMC compared to SA. An artificial neural network (ANN) approach was applied to optimise formulations based on known effective parameters (i.e., mucoadhesive strength, mucoadhesion time and drug release), which proved valuable. This study indicates that an effective buccal tablet formulation of flurbiprofen and lidocaine can be prepared via an optimized ANN approach.

Cellular Evidence of Exosomes in the Reproductive Tract of Chinese Soft-Shelled Turtle Pelodiscus sinensis

The oviduct is a location of egg production, fertilization, and sperm storage. While its secretions have broadly attributes toward different physiological functions. We examined the ultrastructure of oviduct epithelium and glands in relation to the secretions, particularly with exosomes origin in Chinese soft-shelled turtle Pelodiscus sinensis using immunohistochemistry and transmission electron microscopy. The ciliated epithelial and gland cells were involved in the release of exosomes and secretions into lumen throughout the year. The exosomes were either released directly from epithelium or in relation with multivesicular body (MVB). The average size of the particles varies between 50 and 130 nm. These exosomes were also widely distributed in the epithelial ciliated cells and pericytoplasm of glands lumen. Intracellular MVB was characterized by membrane-bounded exosomes of different sizes. Exosomes were also found in close contact with the cilia and sperm membrane in the lumen, which is suggestive of their fusogenic properties. Immunohistochemistry results showed strong to moderate positive expression of exosomes, in ciliated and gland cells, during January, September, and December, as it is the time of sperm storage in this turtle, whereas they showed moderate to weak level of expression during breeding season (May). This is first study about identification of the exosomes in female turtles. Epithelial and glandular exosomes, intracellular MVB, secretions, and secretory vesicles give this turtle specie a unique secretory morphology and a potential model for investigating the secretory nature of the oviduct.

Effect of cellulose acetate phthalate and polyethylene glycol on physical properties and release of theophylline from microcapsules

O presente estudo descreve o desenvolvimento de microcapsulas de teofilina pelo metodo sem adicao de solvente e o efeito da adicao de plastificante na microencapsulacao. A liberacao foi estudada em agua destilada e os dados foram analisados por varios modelos matematicos para determinacao do mecanismo de liberacao. As microcapsulas preparadas mostraram-se esfericas, livres de corrente e com mais de 80% de farmaco encapsulado. O polimero - ftalato de acetato de celulose e o plastificante - polietileno glicol - afetaram as propriedades das microcapsulas, incluindo a liberacao do farmaco (tempo para liberacao de 50% do farmaco, T50). A formulacao com a maior proporcao de polimero e sem plastificante (F3) se mostrou como a de liberacao mais lenta, com T50 = 4,3 h, enquanto as formulacoes com menor proporcao de polimero e 20% de plastificante (m/m) (F13 &14) apresentaram a liberacao mais rapida do farmaco, com T50 de 1,2 h e 1,3 h, respectivamente. A liberacao do farmaco para a maioria das formulacoes seguiu o modelo de Higuchi. Concluiu-se, dos resultados do presente estudo, que o ftalato do acetato de celulose afeta significativamente a liberacao controlada do farmaco em agua, enquanto que a adicao de polietileno glicol aumenta ligeiramente a liberacao do farmaco.