Tahani H. Elfaham

Formulation release characteristics and evaluation of ibuprofen suppositories

Abstract Suppositories of ibuprofen were formulated using cocoa butter, witepsol E 75 and polyethylene glycol (PEG) bases. Cocoa butter suppositories showed the best permeation of the drug (indicated by their k value being the highest) and the fastest dissolution rate. The four PEGs formulae and witepsol followed in order. Ibuprofen in cocoa butter and PEG ‘A’ was physiologically evaluated in albino rats using local vascular permeability and pain sensation as parameters. The results obtained from both methods revealed that cocoa butter was more efficient than PEG as a base for ibuprofen suppositories, in agreement with the in vitro release studies.

Dissolution enhancement of thiacetazone: II — Via ordered mixing technique

Abstract Ordered mixes of thiacetazone were prepared by dry mixing with different water-soluble carriers namely, sodium chloride, potassium chloride, lactose, sorbitol and PEG6000 at 2:1, 1:1, 1:2, 1:5, and 1:9, drug:carrier ratios, in addition to isoniazid at 1:1 and 1:2 drug:isoniazid ratios. A homogeneity test was performed on the resulting mixes. The results obtained from this test indicate that mechanically stable mixes have been formed. The USPXX dissolution test revealed a pronounced increase in the dissolution of thiacetazone from its ordered mixes compared with the dissolution rate of plain drug. However, the ordered mixes with all of the tested carriers except that with sodium chloride showed nearly the same dissolution profile as their corresponding physical mixtures. The effect of carrier particle size and mixing time as well as the carrier type and its ratio, on the degree of homogeneity of the mixes and on the dissolution rate of thiacetazone from these mixes was investigated. Excellent homogeneity of the mixes was seen after mixing for 5 h. The degree of homogeneity of the mixes and drug dissolution rate increased with decreasing particle size of carrier. The dissolution of the drug from mixes containing lower drug level was faster than those containing higher level of the drug. Ordered mixes with sodium chloride gave the fast dissolution rate at 1:9 drug:carrier ratio. At 1:2 ratio, isoniazid gave the highest dissolution rate and excellent homogeneity.

An improved HPLC procedure for the quantitation of diclofenac in plasma

Abstract A rapid, simple and sensitive high performance liquid chromatographic (HPLC) assay for the quantitation of diclofenac (DF) in dog plasma has been developed. Mefenamic acid (MA) was used as the internal standard. After acidification, DF and MA were extracted from plasma into chloroform. Separation was achieved using a C18 reversed phase column. The retention times of DF and MA were 3.8 and 6.3 min., respectively at the flow rate of 1.5 ml/min. The DF interday standard plots (n=4) were highly linear (r>0.99) over the concentration range of 0.01 to 10 μg/ml. DF mean recovery was 98% ± 5.5, and the % CV of intra- and inter-day sample analyses ranged from 2.6 to 10.8% for the entire calibration range. The limit of quantification of DF in plasma was 0.01 μg/ml with the CV of 9.4%. The method was applied for the determination of the pharmacokinetic parameters of DF given by oral and iv bolus administration to dogs.

Factors influencing warfarin response in hospitalized patients.

The objective of this study was to investigate the influence of simultaneous factors that potentially keep patients far from achieving target INR range at discharge in hospitalized patients. Prospective cross-sectional observational study conducted at the Cardiology Department and Intensive Care Unit (ICU) of the Assiut University Hospitals. One-hundred and twenty patients were enrolled in the study from July 2013 to January 2014. Outcome measures were discharge INRs, bleeding and thromboembolic episodes. Bivariate analysis and multinomial logistic regression were conducted to determine independent risk factors that can keep patients outside target INR range. Patients who were newly initiated warfarin on hospital admission were given low initiation dose (2.8 mg ± 0.9). They were more likely to have INR values below 1.5 during hospital stay, 13 (27.7%) patients compared with 9 (12.3%) previously treated patients, respectively (p = .034). We found that the best predictors of achieving below target INR range relative to within target INR range were; shorter hospital stay periods (OR, 0.82 for every day increase [95% CI, 0.72–0.94]), being a male patient (OR, 2.86 [95% CI, 1.05–7.69]), concurrent infection (OR, 0.21 [95% CI, 0.07–0.59]) and new initiation of warfarin therapy on hospital admission (OR, 3.73 [95% CI, 1.28–10.9]). Gender, new initiation of warfarin therapy on hospital admission, shorter hospital stay periods and concurrent infection can have a significant effect on discharge INRs. Initiation of warfarin without giving loading doses increases the risk of having INRs below 1.5 during hospital stay and increases the likelihood of a patient to be discharged with INR below target range. Following warfarin dosing nomograms and careful monitoring of the effect of various factors on warfarin response should be greatly considered.

Assessment of bromhexine hydrochloride formulations in human dry eye patients

Abstract The mucolytic drug bromhexine hydrochloride (BH), was formulated in different ohthalmic dosage forms. The influence of the drug from the different formulations on tear flow rate in humans was investigated. The formulations tested were: BH aqueous solution, methylcellulose and carbopol934 hydrogels; and two polymeric inserts, namely; Gantrez AN 169 (G) and cellulose acetate (CA). The greatest influence on tear production was found using carbopol934. Although both polymeric inserts showed less influence than carbopol934, they sustained the action of BH in the human eye.

Performance of Meloxicam Niosomal Gel Formulations for Transdermal Drug Delivery

Niosomes have been reported as a possible approach to improve low skin permeation shown by conventional vehicles. In this study, a noisome-based delivery system of meloxicam (MX) was developed and characterized for in vitro performance. Niosomes were prepared by reverse-phase evaporation method (REV) using different non ionic surfactants and cholesterol in different molar ratios (1:1, 2:1, 3:1,1: 2 and 1:3) and different drug loading (5, 10 and 15 mg). The used surfactants included Tweens (20, 40 and 80), Brij (35 and 58) and Myrj 52. The prepared systems were characterized for entrapment efficiency, and in-vitro release. Accordingly, selected systems were evaluated for vesicle size, and formulated into different hydrogel bases (sodium carboxymethyl cellulose, hydroxypropyl cellulose, and sodium alginate). Invitro drug release from the different formulations was studied over a period of 8 hr. Effect of formulation additives on drug release was also investigated. The antiinflammatory activity of the selected formulations was evaluated by the paw edema test. Results showed high encapsulation efficiency which ranged from about 81.93% to 99.23%. The highest entrapment efficiency was obtained with 1:1 surfactant: cholesterol ratio and 15 mg drug loading, so niosomes prepared by this ratio were selected for further studies. Particle size ranged from 4.047 to 12.334 μm for different niosomal systems. In vitro drug release from different gel formulations containing 0.3% MX was compared to that from the same formulations containing 0.3% niosomally entrapped drug. In all formulations the drug release was more sustained in case of niosomally entrapped drug. Incorporation of glycerol and propylene glycol as formulation additives into gel formulations markedly enhanced the drug release, but the release from gels containing niosomally entrapped drug was still delayed

Ocular administration of acetazolamide microsponges in situ gel formulations

In the present work, the antiglaucoma drug, acetazolamide, was formulated as microsponges in situ gel for ocular drug delivery aiming an improved therapeutic efficacy and reduction in the systemic side effects of oral acetazolamide. The microsponges were prepared by the quasi emulsion solvent diffusion method and were incorporated into 25% pluronic F-127 in situ gel. Ethyl cellulose polymer in different proportions with drug was used to prepare the microsponges. Different parameters were evaluated to select the best formulation. The formula S2 with drug to polymer ratio (2:1) showed high entrapment efficiency of about 82% and mean particle size of about 10 µm with polydispersity index (PDI) of 0.22, which are suitable characters for ocular delivery. The in situ gels were evaluated for physicochemical properties (pH, gelling capacity, gelation time and rheological properties) and in vivo studies. S2 formulation showed higher therapeutic efficacy compared to free drug in gel. It was non irritant to the rabbits eye. These results indicated that acetazolamide microsponges in situ gel have potential ability for ophthalmic delivery.

Warfarin-drug interactions: An emphasis on influence of polypharmacy and high doses of amoxicillin/clavulanate.

The objective of this study was to investigate the effect of polypharmacy and high doses of amoxicillin/clavulanate on warfarin response in hospitalized patients. This was a prospective cross‐sectional observational study on 120 patients from July 2013 to January 2014. Potentially interacting drugs were classified according to their tendency of increasing international normalized ratio (INR) or bleeding risk. The 87.5% of patients prescribed high‐dose amoxicillin/clavulanate (10–12 g daily) compared with 28.9% of patients prescribed a normal dose (up to 3.6 g daily) had INR values ≥ 4 during the hospital stay (P ≤ .001). Increased number of potentially interacting drugs that are known to increase INR was a significant predictor of having INR values ≥ 4 (OR, 2.5; 95%CI, 1.3–4.7), and increased number of potentially interacting drugs that are known to increase bleeding risk was a significant predictor of experiencing bleeding episodes (OR, 3.1; 95%CI, 1.3–7.3). High doses of amoxicillin/clavulanate were associated with a higher risk of over‐anticoagulation when combined with warfarin than were normal doses. Increased risk of having INR ≥ 4 and bleeding events was associated with increased numbers of potentially interacting drugs prescribed, indicating that polypharmacy is a problem of concern. Frequent monitoring of warfarin therapy along with patients’ medications is necessary to avoid complications.