A Comparative Study on Cyclodextrin Derivatives in Improving Oral Bioavailability of Etoricoxib as a Model Drug: Formulation and Evaluation of Solid Dispersion-Based Fast-Dissolving Tablets.

Etoricoxib, as a model drug, has a poor solubility and dissolution rate. Cyclodextrin derivatives can be used to solve such a problem. A comparative study was run on three cyclodextrin derivatives, namely ß-CD, HP ß-CD, and SBE ß-CD, to solve the drug problem through the formulation of solid dispersions and their preparation into fast-dissolving tablets. Preparations utilized different (1:1, 1:2, and 1:4) drug:carrier ratios. Nine fast-dissolving tablets (containing 1:4 drug: carrier) were formulated using Prosolv ODT® and/or F-melt® type C as super-disintegrants. Optimized formulation was chosen based on a 32 factorial design. The responses chosen were the outcomes of the in vitro evaluation tests. The optimized formulation that had the highest desirability (0.86) was found to be SD-HP3, which was prepared from etoricoxib: HP ß-CD at a 1:4 ratio using equal amounts of Prosolv ODT® and F-melt® type C. An in vivo evaluation of SD-HP3 on a rabbit model revealed its superiority over the marketed product Arcoxia®. SD-HP3 showed a significantly lower Tmax (13.3 min) and a significantly higher Cmax (9122.156 µg/mL), as well as a significantly higher AUC, than Arcoxia®. Thus, the solubility, dissolution, and bioavailability of etoricoxib were significantly enhanced.

Design of taste masked enteric orodispersible tablets of diclofenac sodium by applying fluid bed coating technology.

Diclofenac sodium (DS) a non-steroidal anti-inflammatory drug has a bitter taste and is a local stomach irritant. The aim of this study was to formulate taste masked DS orally dispersible tablets (ODTs) with targeted drug release in the intestine. Pellets of DS were designed using sugar sphere cores layered with DS followed by an enteric coat of Eudragit L100 and a second coat of Eudragit E100 for taste masking. The produced pellets had a high loading efficiency of 99.52% with diameters ranging from 493.7 to 638.9 µm. The prepared pellets were spherical with smooth surfaces on scanning electron microscopy examination. Pellets with the 12% enteric coat Eudragit L100 followed by 5% Eudragit E 100 resulted in 1.4 ±â€¯0.5% DS release in simulated gastric fluid (SGF) and complete dissolution in simulated intestinal fluid (SIF). The pellets were then used to formulate ODTs. In vitro disintegration time of ODTs ranged from 20 ±â€¯0.26 to 46 ±â€¯0.27 s in simulated saliva fluid (SSF). Dissolution was less than 10% in SGF while complete drug release occurred in SIF. The release rate was higher for the optimized formulation (F12) in SIF than for the marketed product Voltaren® 25 mg tablets. The optimized ODTs formulation had a palatable highly acceptable taste.

Counseling and in-advance provision of levonorgestrel emergency contraceptive pills decrease the rate of unplanned pregnancy during breastfeeding: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of counseling and in-advance provision of levonorgestrel emergency contraceptive pills (LNG-ECPs) during postpartum counseling on the incidence of occurrence of unplanned pregnancy during breastfeeding. MATERIALS AND METHODS: The current study is an open-label, parallel, randomized controlled trial carried out in a university hospital in Egypt. All women who delivered and planning to birth-space and breastfeed for at least 1 year were approached for participation during a postpartum hospital stay. Eligible participants were randomly allocated to receive adequate lactational amenorrhea method (LAM) counseling Group 1 (LAM-only) or the above LAM counseling in addition to counseling and in advance provision of one packet of 0.75-mg LNG-ECPs Group 2 (LAM + EC). The two study groups were followed 6 months and the primary outcome was the unplanned pregnancy rate. RESULTS: The study included 2708 women randomized into two groups; LAM-only and LAM + EC groups. Demographic characteristics were homogenous between the groups at the time of recruitment. Unplanned pregnancy was significantly higher in LAM-only group 70 (5.3%) as compared with 5 (0.4%) in LAM-EC group (p = .0001). Also, 619 women (46.6%) used LNG-ECPs with minor side effects like nausea in 175 (28.3%) women, headache in 94 (15.2%) women, vomiting in 24 (3.9%) women. CONCLUSION: In-advance counseling and provision of LNG-ECPs for those opt to use LAM during postpartum family planning counseling can decrease the rate of unplanned pregnancy during breastfeeding and increase the initiation of long-term use of contraception.

Levonorgestrel emergency contraceptive pills use during breastfeeding; effect on infants' health and development.

OBJECTIVE: The current study aims to evaluate the effect of the use of single packet of levonorgestrel emergency contraceptive pills (LNG-ECPs) during breastfeeding on the health and development of the nursing infant. MATERIALS AND METHODS: The current study was an ancillary observational cohort study carried out in a university hospital. We counseled all women delivered and planning birth-space and breastfeed for at least 1 year for participation during postpartum hospital stay. Eligible participants for inclusion in the randomized controlled trial (NCT01111929) were allocated to receive adequate Lactational Amenorrhea Method (LAM) counseling (LAM-only group) or the LAM counseling in addition to counseling about LNG-ECPs use (LAM + emergency contraception (EC) group). These pills were to be used once if unprotected intercourse did occur after expiry of any of the LAM prerequisites and before the couples started to use a reliable method of contraception. We included the first 100 women in the LAM + EC who did use the pills and the first 100 women in the control group who completed the follow-up visits for 6 months to draw the infants' outcome. The primary outcome was the difference of anthropometric measurements of the infants at 3 and 6 months postpartum. Secondary outcome was the difference in the Psycho-social, fine and gross motor, and language development using Denver development screening test. RESULTS: There were no statistical significant differences between both the groups regarding the infants' weight, length, head circumference, chest circumference, and mid-arm circumference at each visit (p > .05). Additionally, there were no statistically significant differences regarding all items (psycho-social, fine and gross motor, and language) of Denver development screening test between the infants in LAM-only and LAM + EC groups (p = .081). CONCLUSIONS: The use of single packet of LNG-ECPs during breastfeeding not objectively affects health and development of nursing infants or subjectively affects the quantity of breast milk.

Role of chitosan on controlling the characteristics and antifungal activity of bioadhesive fluconazole vaginal tablets.

Vaginal fluconazole (FLZ) prolonged release tablets containing chitosan in physical blends with other bioadhesive polymers were designed. Chitosan was mixed with hydroxypropyl methylcellulose (HPMC), guar gum or sodium carboxymethyl cellulose (NaCMC) at different ratios and directly compressed into tablets. In-vitro release profiles of FLZ were monitored at pH 4.8. Compressing chitosan with HPMC at different ratios slowed FLZ release, however, time for 80% drug release (T80) did not exceed 4.3 h for the slowest formulation (F11). Adding of chitosan to guar gum at 1:2 ratio (F3) showed delayed release with T80 17.4 h while, in presence of PVP at 1:2:1 ratio (F5), T80 was 8.8 h. A blend of chitosan and NaCMC at 1:2 ratio (F15) showed prolonged drug release with T80 11.16 h. Formulations F5 and F15 showed fair physical characteristics for the powder and tablets and were subjected to further studies. Fast swelling was observed for F15 that reached 1160.53 ±â€¯13.02% in 4 h with 2 h bioadhesion time to mouse peritoneum membrane compared with 458.83 ±â€¯7.09% swelling with bioadhesion time exceeding 24 h for F5. Extensive swelling of F15 could indicate possible dehydration effect on vaginal mucosa. Meanwhile, antifungal activity against C. albicans was significantly high for F5.

The Development of Self-nanoemulsifying Liquisolid Tablets to Improve the Dissolution of Simvastatin.

The aim of this work was to develop self-nanoemulsifying liquisolid tablets (SNELT) to enhance the dissolution profile of poorly water-soluble simvastatin. SNELT present a unique technique of incorporating self-nanoemulsifying drug delivery systems (SNEDDS) into tablets. Optimized SNEDDS containing different oils, Cremophor® RH 40 (surfactant) and Transcutol® HP (co-surfactant), at different ratios, were used as liquid vehicles and loaded on carrier material, microcrystalline cellulose (MCC), and coating material, Cab-o-sil® H-5 (nanosize colloidal silicon dioxide) powders at different loading factors (L f ) and fixed excipient ratio (R = 20). The effect of using different carrier materials, granulated mannitol, crystalline mannitol, and maltodextrin with MCC at different ratios, and different coating materials, Aeroperl® 300 (granulated silicon dioxide) at different excipient ratios (R), was also emphasized. Liquisolid powders with acceptable flowability, compressibility, and tablet weight were compressed into tablets. Results revealed that powders with L f = 0.2 possessed the most preferable properties to be tableted. SNELT with MCC and Cab-o-sil® H-5 were able to generate nanoemulsions and to enhance the cumulative percent of drug dissolved at 60 min significantly to reach up to 90%. Furthermore, using carrier material (granulated mannitol/MCC at ratio 3:1) enabled SNELT to disperse into nanoemulsion (Z-average = 25.7 nm) and improved the dissolution profile significantly to reach 99% at 60 min. Cab-o-sil® H-5 proved to be a better coating material compared to Aeroperl® 300. In conclusion, developed SNELT were promising in enhancing in vitro dissolution of simvastatin and excipients highly affect SNELT's performance.