Nucleic acid amplification tests in the diagnosis of tuberculous pleuritis: a systematic review and meta-analysis

BACKGROUND: Conventional tests for tuberculous pleuritis have several limitations. A variety of new, rapid tests such as nucleic acid amplification tests – including polymerase chain reaction – have been evaluated in recent times. We conducted a systematic review to determine the accuracy of nucleic acid amplification (NAA) tests in the diagnosis of tuberculous pleuritis. METHODS: A systematic review and meta-analysis of 38 English and Spanish articles (with 40 studies), identified via searches of six electronic databases, hand searching of selected journals, and contact with authors, experts, and test manufacturers. Sensitivity, specificity, and other measures of accuracy were pooled using random effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. Heterogeneity in study results was formally explored using subgroup analyses. RESULTS: Of the 40 studies included, 26 used in-house ("home-brew") tests, and 14 used commercial tests. Commercial tests had a low overall sensitivity (0.62; 95% confidence interval [CI] 0.43, 0.77), and high specificity (0.98; 95% CI 0.96, 0.98). The positive and negative likelihood ratios for commercial tests were 25.4 (95% CI 16.2, 40.0) and 0.40 (95% CI 0.24, 0.67), respectively. All commercial tests had consistently high specificity estimates; the sensitivity estimates, however, were heterogeneous across studies. With the in-house tests, both sensitivity and specificity estimates were significantly heterogeneous. Clinically meaningful summary estimates could not be determined for in-house tests. CONCLUSIONS: Our results suggest that commercial NAA tests may have a potential role in confirming (ruling in) tuberculous pleuritis. However, these tests have low and variable sensitivity and, therefore, may not be useful in excluding (ruling out) the disease. NAA test results, therefore, cannot replace conventional tests; they need to be interpreted in parallel with clinical findings and results of conventional tests. The accuracy of in-house nucleic acid amplification tests is poorly defined because of heterogeneity in study results. The clinical applicability of in-house NAA tests remains unclear

Diagnosis of fallopian tube patency

Objectives: To evaluate and compare the diagnostic value of hysterosalpingography (HSG) and laparoscopic chromopertubation (LCP), in the diagnosis of fallopian tube patency. Design: A comparative prospective study. Setting: The infertility clinic of the Department of Obstetrics and Gynaecology, Ga-Rankuwa hospital (Medical University of Southern Africa), Pretoria, South Africa. Subjects: Fifty patients were initially diagnosed with either unilateral or bilateral tubal block using HSG. Six to eight weeks later the same women were subjected to LCP to assess tubal patency. Main outcome measures: Diagnostic accuracy of HSG to establish tubal patency, site of occlusion and the presence of other pathologies was compared with results obtained after laparoscopic chromopertubation (LCP). Results: Hysterosalpingography diagnosed bilateral proximal, bilateral distal and mixed (i.e. one side proximal and the other distal) tubal occlusion in 15(40.5%); 13(35.1%) and five (13.5%) cases respectively. Diagnostic laparoscopy confirmed the above sites of occlusion in nine (24.3%), 71(45.9%) and three (8.1%) cases. Laparoscopy detected bilateral tubal patience in three (8.1%) patients, in whom HSG had diagnosed tubal occlusion. USG was able to detect peritubal adhesion in only four (10.8%) patients as compared with 11 patients when LCP procedure was used. In comparison with HCP, hysterosalpingography demonstrated 70% specificity for accurately diagnosing proximal tubal occlusion. Conclusion: On a comparative scale, HSG demonstrated reduced positive predictive value especially for bilateral proximal tubal occlusion. However, in spite of its relatively limited value for accurately identifying tubal patency, HSG should still serve as a useful primary investigation. East African Medical Journal Vol. 82(9) 2005: 457-46

Smart nanocrystals of artemether: fabrication, characterization, and comparative in vitro and in vivo antimalarial evaluation

Syed Muhammad Hassan Shah,1 Farhat Ullah,2 Shahzeb Khan,2,3 Syed Muhammad Mukarram Shah,4 Marcel de Matas,5 Zahid Hussain,6 Muhammad Usman Minhas,7 Naser M AbdEl-Salam,8 Khaled Hafez Assi,3 Mohammad Isreb3 1Department of Pharmacy, Sarhad University of Science & Information Technology, Peshawar, 2Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 3Institute of Life Sciences Research, School of Pharmacy, University of Bradford, West Yorkshire, 4Department of Pharmacy, University of Swabi, KPK, Pakistan; 5SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK; 6Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi MARA, Selangor, Malaysia; 7Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur Pakistan, Bahawalpur, Pakistan; 8Riyadh Community College, King Saud University, Riyadh, Saudi Arabia Abstract: Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena® DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena® DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities. Keywords: artemether, milling, smart nanocrystals, nanosuspension, in vitro dissolution, antimalarial activit

A new strategy for taste masking of azithromycin antibiotic: development, characterization, and evaluation of azithromycin titanium nanohybrid for masking of bitter taste using physisorption and panel testing studies

Fazli Amin,1 Shahzeb Khan,1,2 Syed Muhammad Hassan Shah,3 Haroon Rahim,3 Zahid Hussain,4 Muhammad Sohail,5 Riaz Ullah,6,7 Mansour S Alsaid,6 Abdelaaty A Shahat6,8 1Department of Pharmacy, University of Malakand, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu Natal, Westville 4000, Durban South Africa; 3Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan; 4Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi MARA, Selangor, Malaysia; 5Department of Pharmacy, COMSATS, Abbottabad, Khyber Pakhtunkhwa, Pakistan; 6Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 7Department of Chemistry, Government College Ara Khel FR, Kohat, Khyber Pakhtunkhwa, Pakistan; 8Phytochemistry Department, National Research Centre, Dokki, Giza, Egypt Background: The obnoxious bitter taste of orally taken antibiotics is one of the biggest problems in the treatment of children. The pediatric population cannot tolerate the bitter taste of drugs and vomit out which ultimately leads to suboptimal therapeutic value, grimace and mental stress so it is the challenging task for the formulation scientists to formulate a palatable formulation particularly to overcome address the issue. Purpose of study: The study aimed to mask and evaluate the unpleasant bitter taste of azithro­mycin (AZ) in the dry suspension dosage form by physisorption technique. Materials and methods: AZ was selected as an adsorbent and titanium dioxide nanoparticles as adsorbate. The AZ nanohybrids (AZN) were prepared by treating fixed amount of adsorbent with a varied amount of adsorbate, prepared separately by dispersing it in an aqueous medium. The mixture was sonicated, stirred followed by filtration and drying. The AZN produced were characterized by various techniques including scanning electron microscopy (SEM), energy dispersive X-rays (EDX), powder X-ray diffraction (PXRD), HPLC and Fourier-transformed infrared (FTIR). The optimized nanohybrid was blended with other excipients to get stable and taste masked dry suspension dosage form.Results: The results confirmed the adsorption of titanium dioxide nanoparticles on the surface of AZ. The fabricated optimized formulation was subjected for taste masking by panel testing and accelerated stability studies. The results showed a remarkable improvement in bitter taste masking, inhibiting throat bite without affecting the dissolution rate. The product showed an excellent stability both in dry and reconstituted suspension. The optimized formulation of AZN and was found stable when subjected to physical and chemical stability studies, this is because of short and single step process which interns limits the exposure of the product to various environmental factors that could potentially affect the stability of the product. The dissolution rate of the optimized formulation of AZN was compared with its marketed counterpart, showing the same dissolution rate compared to its marketed formulation.Conclusion: The current study concludes that, by fabricating AZ-titanium nanohybrids using physisorption can effectively mask the bitter taste of the drug. The palatability and stability of azithromycin formulation was potentially enhanced without affecting its dissolution rate. Keywords: azithromycin, AZ, titanium dioxide nanoparticles, TNPs, azithromycin–TiO2 nanohybrid, AZN, dissolution, physisorption&nbsp

Aceclofenac nanocrystals with enhanced in vitro, in vivo performance: formulation optimization, characterization, analgesic and acute toxicity studies

Haroon Rahim,1 Abdul Sadiq,1 Shahzeb Khan,1 Mir Azam Khan,1 Syed Muhammad Hassan Shah,2 Zahid Hussain,3 Riaz Ullah,4 Abdelaaty Abdelaziz Shahat,4,5 Khalid Ibrahim6 1Department of Pharmacy, University of Malakand, Chakdara, 2Department of Pharmacy, Sarhad University of Science and Information Technology Peshawar, Khyber Pakhtunkhwa, Pakistan; 3Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi, Mara, Selangor, Malaysia; 4Department of Pharmacognosy and Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Phytochemistry Department, National Research Center, Dokki, Giza, Egypt; 6Department of Chemical Engineering, College of Engineering, Al-Muzahmeiah Branch, King Saud University, Riyadh, Saudi Arabia Abstract: This study was aimed to enhance the dissolution rate, oral bioavailability and analgesic potential of the aceclofenac (AC) in the form of nanosuspension using cost-effective simple precipitation–ultrasonication approach. The nanocrystals were produced using the optimum conditions investigated for AC. The minimum particle size (PS) and polydispersity index was found to be 112±2.01 nm and 0.165, respectively, using hydroxypropyl methylcellulose (1%, w/w), polyvinylpyrrolidone K30 (1%, w/w) and sodium lauryl sulfate (0.12%, w/w). The characterization of AC was performed using zeta sizer, scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The saturation solubility of the AC nanocrystals was substantially increased 2.6- and 4.5-fold compared to its unprocessed active pharmaceutical ingredient in stabilizer solution and unprocessed drug. Similarly, the dissolution rate of the AC nanocrystals was substantially enhanced compared to its other counterpart. The results showed that >88% of AC nanocrystals were dissolved in first 10 min compared to unprocessed AC (8.38%), microsuspension (66.65%) and its marketed tablets (17.65%). The in vivo studies of the produced stabilized nanosuspension demonstrated that the Cmax were 4.98- and 2.80-fold while area under curve from time of administration to 24 h (AUC0→24 h) were found 3.88- and 2.10-fold greater when compared with unprocessed drug and its marketed formulation, respectively. The improved antinociceptive activity of AC nanocrystals was shown at much lower doses as compared to unprocessed drug, which is purely because of nanonization which may be attributed to improved solubility and dissolution rate of AC, ultimately resulting in its faster rate of absorption. Keywords: aceclofenac nanocrystals, precipitation–ultrasonication, dissolution rate, in vivo studie

Experimental and molecular modeling approach to optimize suitable polymers for fabrication of stable fluticasone nanoparticles with enhanced dissolution and antimicrobial activity

Shaimaa Ahmed,1 Thirumala Govender,1 Inamullah Khan,2 Nisar ur Rehman,2 Waqar Ali,2 Syed Muhammad Hassan Shah,3 Shahzeb Khan,4 Zahid Hussain,5 Riaz Ullah,6,7 Mansour S Alsaid6 1Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 2Department of Pharmacy, COMSATS Institute of Information Technology (CIIT), Abbotabad, 3Department of Pharmacy, Sarhad University of Science and Technology, Peshawar, 4Department of Pharmacy, University of Malakand Dir (Lower), Chakdara, Khyber Pakhtunkhwa, Pakistan; 5Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi Mara, Puncak Alam, Selangor, Malaysia; 6Department of Pharmacognosy and Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 7Department of Chemistry, Government College Ara Khel FR, Kohat, Khyber Pakhtunkhwa, Pakistan Background and aim: The challenges with current antimicrobial drug therapy and resistance remain a significant global health threat. Nanodrug delivery systems are playing a crucial role in overcoming these challenges and open new avenues for effective antimicrobial therapy. While fluticasone (FLU), a poorly water-soluble corticosteroid, has been reported to have potential antimicrobial activity, approaches to optimize its dissolution profile and antimicrobial activity are lacking in the literature. This study aimed to combine an experimental study with molecular modeling to design stable FLU nanopolymeric particles with enhanced dissolution rates and antimicrobial activity. Methods: Six different polymers were used to prepare FLU nanopolymeric particles: hydroxyl propyl methylcellulose (HPMC), poly (vinylpyrrolidone) (PVP), poly (vinyl alcohol) (PVA), ethyl cellulose (EC), Eudragit (EUD), and Pluronics®. A low-energy method, nanoprecipitation, was used to prepare the polymeric nanoparticles. Results and conclusion: The combination of HPMC-PVP and EUD-PVP was found most effective to produce stable FLU nanoparticles, with particle sizes of 250 nm ±2.0 and 280 nm ±4.2 and polydispersity indices of 0.15 nm ±0.01 and 0.25 nm ±0.03, respectively. The molecular modeling studies endorsed the same results, showing highest polymer drug binding free energies for HPMC-PVP-FLU (-35.22 kcal/mol ±0.79) and EUD-PVP-FLU (-25.17 kcal/mol ±1.12). In addition, it was observed that Ethocel® favored a wrapping mechanism around the drug molecules rather than a linear conformation that was witnessed for other individual polymers. The stability studies conducted for 90 days demonstrated that HPMC-PVP-FLU nanoparticles stored at 2°C–8°C and 25°C were more stable. Crystallinity of the processed FLU nanoparticles was confirmed using differential scanning calorimetry, powder X-ray diffraction analysis and TEM. The Fourier transform infrared spectroscopy (FTIR) studies showed that there was no chemical interaction between the drug and chosen polymer system. The HPMC-PVP-FLU nanoparticles also showed enhanced dissolution rate (P<0.05) compared to the unprocessed counterpart. The in vitro antibacterial studies showed that HPMC-PVP-FLU nanoparticles displayed superior effect against gram-positive bacteria compared to the unprocessed FLU and positive control. Keywords: fluticasone, nanoparticles, drug delivery systems, antimicrobial, molecular modeling, molecular dynamic