Optimization of a Novel Oral Colon Delivery System of Indomethacin Using Full Factorial Design

Purpose: To develop and optimize indomethacin (IDM) matrix tablets for specific colon drug delivery.Methods: Indomethacin matrix tablets containing hydrogenated castor oil (HCO), and pectin (PEC) were prepared by hot fusion method. A 32 full factorial design was used to investigate the combined effect of two independent formulation variables, X1 and X2, namely, the amount of HCO and PEC, respectively. Their effect on IDM release from the matrix tablets in acidic medium (0.1 N HCl) and phosphate buffer (pH 6.8), were analyzed and optimized. A contour plot was also applied to graphically represent the effect of the independent variables on drug release in pH 6.8 medium at 2 h (Y1) and 24 h (Y2), and the time required for 25 % drug release (Y3) as dependent variables.Results: The optimized IDM matrix tablets showed almost total retardation of drug release in acidic medium and prolonged sustained release in pH 6.8 medium over 24 h. The correlation coefficient (R2) value for Y1, Y2 and Y3 were 0.99850, 0.9980 and 0.9970, respectively, indicating good correlation between dependent and independent variables. Differences between the coefficients for Y1, Y2 and Y3 were significant (p < 0.05), and hence contributed significantly to the prediction of the independent variables.Conclusion: The findings indicate that successful design, development, and optimization of IDM matrix tablets for colon delivery has been achieved.Keywords: Indomethacin, Hydrogenated castor oil, Pectin, Factorial design, Matrix tablets, Colondelivery syste

Nanosuspension: An Emerging Trend for Bioavailability Enhancement of Etodolac

Etodolac (ET) (poorly soluble drug) nanosuspensions were prepared by both pH shift method and antisolvent techniques in order to increase its dissolution rate. Various stabilizers were used, namely, Tween 20 and 80, HPMC, PVP K44, PVA, PEG 400, NaCMC, and β-cyclodextrin. The prepared nanosuspensions were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) and evaluated for their particle size, particle size distribution, and in vitro dissolution rate. In general, it was found that the antisolvent method for the preparation of ET nanosuspensions reduced the drug particle size to a higher extent compared to the pH shift method. The dissolution rate of ET in distilled water was markedly enhanced in the nanosized system, as more than 65% of drug dissolved in 10 min from all the nanosuspension formulations except F5 (stabilized with PVP K44) and F8 (stabilized with Tween 20), as compared to less than 20% of crude drug. Nanoparticles prepared by antisolvent method using Tween 80 as a stabilizer were selected for further in vivo study. The in vivo test demonstrated that nanoparticles of ET were well absorbed with a percentage drug absorption value 2.7 times more than that of micrometric size of crude ET

A Promising Approach to Provide Appropriate Colon Target Drug Delivery Systems of Vancomycin HCL: Pharmaceutical and Microbiological Studies

Vancomycin HCl was prepared as orally administered colon target drug delivery tablets for systemic therapy. Tablet matrices containing 10–60% of tablet weight of guar gum (F1–F6) were prepared by direct compression and subjected to in vitro release studies to explore their sustained release in the colon. Various synthetic and natural polymers were incorporated to F6 to modify the drug release rate. Different 15 matrix tablet formulations (F6–F20) were enteric coated with hydroxypropyl methyl cellulose phthalate. F6, F13 and F20 showed promising sustained release results having median dissolution time (MDT) values: 8.25, 7.97, and 7.64, respectively. Microbiological assay was performed to test the efficacy of F6, F13, and F20 to inhibit clinical Staphylococcus aureus (SA) isolates. Bactericidal activity of F6 was reached after 2, 4, and 24 hours of incubation against MSSA 18, MRSA 29, and MRSA 11 strains, respectively, while it was reached within 6–8 hours in case of F13, and F20 against all strains tested. F13 enhanced log microbial reduction by 1.74, 0.65 and 2.4 CFU/mL compared to F6 while it was 1, 2.57 and 1.57 compared to F20 against MSSA18, MRSA11 and MRSA29, respectively. Vancomycin HCl tablets displayed a promising sustained release in vitro and microbiological inhibitory action on all isolates tested

Newly Developed Topical Cefotaxime Sodium Hydrogels: Antibacterial Activity and In Vivo Evaluation

In an attempt to reach better treatment of skin infections, gel formulations containing Cefotaxime (CTX) were prepared. The gel was formulated using Carbopol 934 (C934), Hydroxypropyl Methylcellulose 4000 (HPMC 4000), Carboxymethylcellulose Sodium (Na CMC), Pectin (PEC), Xanthan Gum (XG), or Guar Gum (GG). Thirteen different formulas were prepared and characterized physically in terms of color, syneresis, spreadability, pH, drug content, and rheological properties. Drug-excipients compatibility studies were confirmed by FTIR and then in vitro drug release study was conducted. In vitro and in vivo antibacterial activities of CTX were studied against wound pathogens such as, Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa), using either pure drug or Fucidin® cream as control. F13 provides better spreadability compared to F1 (XG) or F11 (HPMC). Moreover, the release of the drug from hydrogel F13 containing C934 was slower and sustained for 8 h. Stability study revealed that, upon storage, there were no significant changes in pH, drug content, and viscosity of the gels. Also, F13 showed the larger inhibition zone and highest antibacterial activity among other formulations. Histological analysis demonstrated that after single treatment with F13 gel formulation, a noticeable reduction in microbial bioburden occurred in case of both Gram positive and Gram negative bacterial isolates

Formulation of Indomethacin Colon Targeted Delivery Systems Using Polysaccharides as Carriers by Applying Liquisolid Technique

The present study aimed at the formulation of matrix tablets for colon-specific drug delivery (CSDD) system of indomethacin (IDM) by applying liquisolid (LS) technique. A CSDD system based on time-dependent polymethacrylates and enzyme degradable polysaccharides was established. Eudragit RL 100 (E-RL 100) was employed as time-dependent polymer, whereas bacterial degradable polysaccharides were presented as LS systems loaded with the drug. Indomethacin-loaded LS systems were prepared using different polysaccharides, namely, guar gum (GG), pectin (PEC), and chitosan (CH), as carriers separately or in mixtures of different ratios of 1 : 3, 1 : 1, and 3 : 1. Liquisolid systems that displayed promising results concerning drug release rate in both pH 1.2 and pH 6.8 were compressed into tablets after the addition of the calculated amount of E-RL 100 and lubrication with magnesium stearate and talc in the ratio of 1 : 9. It was found that E-RL 100 improved the flowability and compressibility of all LS formulations. The release data revealed that all formulations succeeded to sustain drug release over a period of 24 hours. Stability study indicated that PEC-based LS system as well as its matrix tablets was stable over the period of storage (one year) and could provide a minimum shelf life of two years

Adherence to Mirror Image Hierarchy: Evidence from Modern Standard and Libyan Arabic

Referring to a specific object sometimes requires using several modifiers, such as adjectives with nouns to describe objects. The ordering of these adjectives is generally assumed to adhere to universal hierarchies. It is, therefore, predicted that prenominal (e.g. English) languages present preferred ordering, and postnominal (Arabic) languages are further expected to mirror the ordering observed in those prenominal languages. This paper investigates these predictions by providing a quantitative account of internal orderings of elements in some Arabic noun phrases in Modern Standard Arabic (MSA) and Libyan Arabic (LA). The primary concern is with the relative ordering of adjectives, where both semantic adjective classes and functions (specifying~descriptive~classifying) are invoked. The study findings showed ordering preference in both MSA and LA, at both the global and refined functional levels, in line with the suggested hierarchies. Deviation from the preferred order also appeared possible but under certain circumstances which appear at a greater level in LA than MSA. These instances were, however, accounted for through factors such as contrastive environments