Reliability Analysis of the New Exponential Inverted Topp-Leone Distribution with Applications.

The inverted Topp-Leone distribution is a new, appealing model for reliability analysis. In this paper, a new distribution, named new exponential inverted Topp-Leone (NEITL) is presented, which adds an extra shape parameter to the inverted Topp-Leone distribution. The graphical representations of its density, survival, and hazard rate functions are provided. The following properties are explored: quantile function, mixture representation, entropies, moments, and stress-strength reliability. We plotted the skewness and kurtosis measures of the proposed model based on the quantiles. Three different estimation procedures are suggested to estimate the distribution parameters, reliability, and hazard rate functions, along with their confidence intervals. Additionally, stress-strength reliability estimators for the NEITL model were obtained. To illustrate the findings of the paper, two real datasets on engineering and medical fields have been analyzed.

Multiple response optimization of processing and formulation parameters of Eudragit RL/RS-based matrix tablets for sustained delivery of diclofenac.

CONTEXT: Multiple response optimization is an efficient technique to develop sustained release formulation while decreasing the number of experiments based on trial and error approach. OBJECTIVE: Diclofenac matrix tablets were optimized to achieve a release profile conforming to USP monograph, matching Voltaren®SR and withstand formulation variables. The percent of drug released at predetermined multiple time points were the response variables in the design. Statistical models were obtained with relative contour diagrams being overlaid to predict process and formulation parameters expected to produce the target release profile. MATERIALS AND METHODS: Tablets were prepared by wet granulation using mixture of equivalent quantities of Eudragit RL/RS at overall polymer concentration of 10-30%w/w and compressed at 5-15KN. RESULTS AND DISCUSSION: Drug release from the optimized formulation E4 (15%w/w, 15KN) was similar to Voltaren, conformed to USP monograph and found to be stable. Substituting lactose with mannitol, reversing the ratio between lactose and microcrystalline cellulose or increasing drug load showed no significant difference in drug release. Using dextromethorphan hydrobromide as a model soluble drug showed burst release due to higher solubility and formation of micro cavities. CONCLUSION: A numerical optimization technique was employed to develop a stable consistent promising formulation for sustained delivery of diclofenac.

STUDYING THE IMPACT OF FORMULATION AND PROCESSING PARAMETERS ON THE RELEASE CHARACTERISTICS FROM HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF DICLOFENAC.

Hydrophilic matrices, especially HPMC based, are widely used to provide sustained delivery where drug release occurs mainly by diffusion. A 3(2) full factorial design was used to develop and evaluate HPMC matrix tablet for sustained delivery of diclofenac. The influences of polymer concentration/viscosity, diluent type/ratio, drug load/solubility, compression force and pH change on drug release were investigated. Ten tablet formulations were prepared using wet granulation. HPMC K15M (10-30% w/w) was used as the polymer forming matrix. The release kinetics, compatibility studies, lot reproducibility and effect on storage were discussed. Increasing polymer concentration and compression force showed antagonistic effect on release rate. Mannitol tends to increase release rate more than lactose. Reversing diluent ratio between lactose and MCC did not affect drug release. Changing pH resulted in burst release whereas drug solubility is pH independent. F1 showed similar release to Voltaren SR and followed Higuchi model. Drug and polymer were compatible to each other. The formulation is stable at long and intermediate conditions with a significant increase in release rate at accelerated conditions due to water uptake and polymer swelling. The developed formulation was successful for a sustained delivery of diclofenac.

Evaluation of biodegradable polyester-co-lactone microparticles for protein delivery.

Abstract Poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) was previously evaluated for the colloidal delivery of α-chymotrypsin. In this article, the effect of varying polymer molecular weight (MW) and chemistry on particle size and morphology; encapsulation efficiency; in vitro release; and the biological activity of α-chymotrypsin (α-CH) and lysozyme (LS) were investigated. Microparticles were prepared using emulsion solvent evaporation and evaluated by various methods. Altering the MW or monomer ratio of PGA-co-PDL did not significantly affect the encapsulation efficiency and overall poly(1,3-propanediol adipate-co-ω-pentadecalactone) (PPA-co-PDL) demonstrated the highest encapsulation efficiency. In vitro release varied between polymers, and the burst release for α-CH-loaded microparticles was lower when a higher MW PGA-co-PDL or more hydrophobic PPA-co-PDL was used. The results suggest that, although these co-polyesters could be useful for protein delivery, little difference was observed between the different PGA-co-PDL polymers and PPA-co-PDL generally provided a higher encapsulation and slower release of enzyme than the other polymers tested.

An experimental study to measure oil recovery factor by chemical agents and carbon dioxide after waterflooding.

Development of tight formations would be one of the main priority for petroleum industries due to the enormous demand to the fossil fuels in various industries. In this paper, we provided a set of experiments on the generated foams by carbon dioxide (CO2) and nitrogen (N2), cyclic CO2 injection, water alternating gas injection (WAG), active carbonated water injection (coupling surfactant effects and carbonated water (CW)), and introducing the impact of active carbonated water alternating gas injection (combination of WAG and CW injection) after waterflooding. Carbon dioxide is more feasible than nitrogen, it can be mobilize more in the pore throats and provided higher oil recovery factor. Generated foam with CO2 has increased oil recovery factor about 32% while it's about 28% for generated foam by N2. Moreover, according to the results of this study, the maximum oil recovery factor for active carbonated water alternating gas injection, active carbonated water injection, and water alternating gas injection measured 74%, 65%, and 48% respectively.

Incidence, stability and risk assessment for sulfonamides and tetracyclines in aqua-cultured Nile Tilapia fish of Egypt.

The current study was conducted to determine sulfonamides (SAs) and tetracyclines (TCs) residuals in farmed Nile Tilapia fish (Orechromis niloticus) using the solid phase extraction (SPE) technique and high performance liquid chromatography with diode array detection (HPLC-DAD). As well, to assess the potential health risk due to the consumption of contaminated fish following its household thermal processing. Tilapia samples were collected from four governorates in Egypt; El-Fayoum, Giza, Cairo, and Alexandria. The results showed that 56.3 % (27 out of 48 samples) of fish samples were free of antibiotics, while 10.4 % and 33.3 % of samples were contaminated by SAs and TCs, respectively. Besides, oxytetracycline (OTC) showed the highest detected concentrations ranged from 52.8 to 658.5 (µg/kg), followed by chlortetracycline (OTC) (35.89-109.76 µg/kg), and tetracycline (TC) (68.8-96.7 µg/kg). While the detected SAs were between 32.89 µg/kg (sulfamethazine: SMT) and 136.43 µg/kg (sulfadimethoxine: SDM). As well, sulfamethoxazole (SMX) showed an average concentration of 52.41 µg/kg. Notably, only 7 samples (out of 21 positive samples) had residual levels exceeded the permissible limits. The study also concluded that freezing fish at -18 °C for one week had no significant effect on the stability of SAs and TCs. As well, SAs showed more stability than TCs against the thermal processing for fish. Indeed, the stability of SAs and TCs antibiotics was arranged in a descending order, shown as follows: SMT > SDM > SMX > CTC > TC > OTC. Eventually, no potential risk to the Egyptian population was found from the consumption of the contaminated fish samples by SAs and TCs.

Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery.

Nanoliposomes have an organized architecture that provides versatile functions. In this study, liposomes were used as an ocular carrier for nanogold capped with flucytosine antifungal drug. Gold nanoparticles were used as a contrasting agent that provides tracking of the drug to the posterior segment of the eye for treating fungal intraocular endophthalmitis. The nanoliposomes were prepared with varying molar ratios of lecithin, cholesterol, Span 60, a positive charge inducer (stearylamine), and a negative charge inducer (dicetyl phosphate). Formulation F6 (phosphatidylcholine, cholesterol, Span 60, and stearylamine at a molar ratio of 1:1:1:0.15) demonstrated the highest extent of drug released, which reached 7.043 mg/h. It had a zeta potential value of 42.5±2.12 mV and an average particle size approaching 135.1±12.0 nm. The ocular penetration of the selected nanoliposomes was evaluated in vivo using a computed tomography imaging technique. It was found that F6 had both the highest intraocular penetration depth (10.22±0.11 mm) as measured by the computed tomography and the highest antifungal efficacy when evaluated in vivo using 32 infected rabbits' eyes. The results showed a strong correlation between the average intraocular penetration of the nanoparticles capped with flucytosine and the percentage of the eyes healed. After 4 weeks, all the infected eyes (n=8) were significantly healed (P<0.01) when treated with liposomal formulation F6. Overall, the nanoliposomes encapsulating flucytosine have been proven efficient in treating the infected rabbits' eyes, which proves the efficiency of the nanoliposomes in delivering both the drug and the contrasting agent to the posterior segment of the eye.

Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride.

PURPOSE: The aim of the present study was to improve the bioavailability of itopride (ITO) and sustain its action by formulating as a floating dosage form. MATERIALS AND METHODS: Sustained-release floating tablets of ITO hydrochloride (HCl) were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol). Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. RESULTS: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031). The pharmacokinetic results indicated that the area under the curve (AUC0-∞) of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton®) and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022). CONCLUSION: The prepared floating tablets of ITO HCl (F10) could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability.

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study.

BACKGROUND: The blood-brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. METHODS: Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione-modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. RESULTS: The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than -65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. CONCLUSION: Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections.

Estradiol-progesterone interaction during the preparation of vaginal rings.

An unexpected enhanced release, in vitro, of estradiol (E2) was observed on the preparation of vaginal rings containing E2 and progesterone (P) in a silicone elastomer. The present work deals with exploring the reason(s) behind this enhanced E2 release. The effect of the ring design (i.e., putting P and E2 in the same compartment or in adjacent or separate compartments) was studied. The effects of the curing temperature as well as the curing time were also investigated. The possible interaction(s) between P and E2 on simple heating of their mixtures was investigated using infrared (IR), differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR) techniques. Also, the dissolution behavior of P, E2, and their mixture before and after heating was studied. The ring design, with respect to the position of the steroid layer(s), affected the release of P and E2 from the vaginal rings. Curing the rings at higher temperatures (>/=140 degrees C) for >/=30 min resulted in an enhanced release of the steroids, especially E2. The IR, DSC, phase diagram, and NMR results indicate that an interaction between P and E2, leading to the formation of a molecular complex, took place. It was concluded that putting P and E2 in the same compartment and curing by heating at a high temperature and for an extended time promoted this kind of interaction. The greater hydrophobicity of the interaction product, relative to that of E2, was considered the main reason behind the enhanced in vitro release of E2 from the vaginal rings.

Malaria parasitemia during delivery.

OBJECTIVE: The aim of this study is to investigate the impact of plasmodium falciparum infection in parturient women in Central Sudan where malaria transmission is mesoendemic. The purpose of this paper is to find out the prevalence of malaria parasitemia and the risk of anemia among parturient women and to suggest appropriate strategies to lower their prevalence rates. METHODS: This prospective study was conducted at Medani Teaching Hospital, Sudan, a tertiary regional referral center, during the period January 1997 through to December 1997. All cases were admitted during labor to the delivery room and were clinically suspected to have malaria. History, examination and investigations were carried out on all patients. RESULTS: The total number of patients enrolled in this study was 550, amounting to 14.9% of all women (N=3,687) who delivered during the study period. The prevalence of malaria parasitemia was 58.9% (N=550) while prevalence of anemia (defined as hemoglobulin <9.0 g/dl) was 24.1%. The mean hemoglobulin levels in patients with positive and negative malaria parasitemia was 9.72 1.62 and 9.85 1.60 g/dl. Statistically the difference in the mean hemoglobulin level was not significant, t=0.879, (P>0.05). A significant negative correlation between parasite count in maternal blood and hemoglobulin level of the mother, was observed, where r=-0.121 (P=0.032). Out of 17 (3.3%) patients who had used chloroquine tablets for prophylaxis, 11 patients still had positive parasitemia. Although there was a higher parasite count in those 11 patients, statistically the difference was not significance where P> 0.05. CONCLUSION: The study documents a high prevalence of malaria parasitemia and anemia among the parturient women in Central Sudan. There were 533 pregnant women (97%) who did not use chloroquine tablets as chemoprophylaxis and 17 (3%) had prophylaxis. Eleven of the later (N=17) had positive parasitemia. In view of the high prevalence of parasitemia and anemia, and although the sample of patients who used chloroquine tablets for prophylaxis and had positive parasitemia is small (17 out of 550), a wide scale prophylaxis placebo-controlled trial is recommended to test the impact of prophylactic drugs in pregnancy and to measure the effect on the mother, and the neonate. The drug that proves to be effective as a prophylactic, should be an integral part of ante-natal care along with iron and folic acid as anti-anemic therapy. Moreover, prompt treatment of malaria infection with the appropriate anti-malarial drug, spray of insecticides and the use of insecticide-impregnated bed-nets and curtains for preventing malaria are recommended.

Comparative study of itraconazole-cyclodextrin inclusion complex and its commercial product.

Itraconazole (ITZ) solid complex using hydroxypropyl-beta-cyclodextrin (ITZ-HP-beta-CD) with 20% polyvinylpyrrolidone was prepared by a co-evaporation method. The complex improved antifungal activity against C. parapasilosis and C. albicans. The complex demonstrated good flow and compressibility characteristics. The complex was formulated as a capsule dosage form and drug release was evaluated. Capsules containing ITZ-HP-beta-CD at a molar ratio of 1:3 with 20% polyvinylpyrrolidone have a faster dissolution rate than commercial capsules (Sporanox). About 88% of ITZ was released in less than 30 min and the initial dissolution rate exhibited a 3.5-fold increase compared to the commercial product. UV spectrophotometeric, HPLC, and antimicrobial methods were used to determine ITZ concentration in the release medium and the results obtained by these methods are reported. It was found that HPLC analysis is a suitable and reliable method for determination of the drug concentration with a coefficient of variation less than 10%. The intraday precision showed a coefficient of variation less than 3.96%, and that for interday was less than 4.99%. The HPLC method was more accurate and precise than the antimicrobial and UV-spectrophotometric methods for determination of ITZ concentration present in the release medium.