Formulation and evaluation of Buccal mucoadhesive tablets of diclofenac sodium using 23 factorial designs

Buccal tablets

Diclofenac sodium

Drug release

Mucoadhesion

Mucoadhesive tablets

Release kinetics

Development, in-vitro and ex-vivo evaluation of muco-adhesive buccal tablets of hydralazine hydrochloride

Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.

Comparison on radiation dose of direct aspiration one-time thrombectomy and stent thrombectomy in treatment of acute middle cerebral artery occlusion / 中国介入影像与治疗学

Objective: To compare the radiation dose of direct aspiration first-pass thrombectomy (ADAPT) and conventional stent thrombectomy in treatment of acute middle cerebral artery occlusion. Methods: Totally 54 middle cerebral artery occlusion patients were retrospectively analyzed. The patients were divided into ADAPT group (n=29) and stent group (conventional stent removal, n=25) according to interventional treatment method. The intraoperative fluoroscopy time, air kerma (AK), dose area product (DAP), the number of photographic sequences and photographic frames were recorded and compared between 2 groups, and the correlations of the above indicators were analyzed. Results: The fluoroscopy time, AK, DAP, the number of photographic sequences and photographic frames in ADAPT group were all lower than those in stent group (all P<0.05). There were 25 cases (25/29, 86.21%) in ADAPT group and 13 cases (13/25, 52.00%) in stent group AK value <1.0 Gy, and the rate of patients with DAP value <1.0 Gy in ADAPT group was higher than that in stent group (P<0.01). There were 22 cases (22/29, 75.86%) in ADAPT group and 11 cases (11/25, 44.00%) in stent group DAP value <100 Gy•cm2, and the rate of patients with DAP value <100 Gy•cm2 in ADAPT group was higher than that in stent group (P=0.01). The fluoroscopy time was positively correlated with DAP (r=0.60, P<0.01) and AK (r=0.69, P<0.01), so was DAP and AK (r=0.81, P<0.01). Conclusion: The radiation dose of ADAPT technology was lower than conventional stent removal for treatment of acute middle cerebral artery occlusion.

Evidence of Subclavian Vein Thrombosis on First-Pass ¹⁸FDG PET in a Patient with Relapsing Upper Mediastinum Lymphoma / 대한핵의학회잡지

Baseline ¹⁸F-FDG PET was performed in a 74-year-old patient with relapsing upper mediastinum lymphoma. Left subclavian thrombosis was suspected on prior contrast-enhanced CT. Dynamic PET imaging was achieved during 3 min after IV injection of ¹⁸F-FDG to the left arm in order to further assess left subclavian vein permeability. The 20-s dynamic frame at 1 min after injection confirmed the absence of flow in the left subclavian vein and evidenced the derivation of ¹⁸F-FDG through left axillary, then superficial, then right internal mammary collaterals to the superior vena cava, hence confirming the subclavian thrombosis.

Study on the First-Pass Effects of Vitexin-4′-O-Glucoside in Rats in vivo / 中国药房

OBJECTIVE:To investigate the first-pass effect and mechanism of vitexin-4′-O-glucoside(VG)in rats so as to pro-vide a basis for new drug development. METHODS:10 SD rats were divided into a group of hepatic portal venous administration and a group of femoral venous administration,which respectively received VG iv at superior mesenteric vein and femoral vein,and then metabolic rate was calculated by finding out the AUC of VG in the rats’livers. 15 SD rats were divided into a group of gastric infusion,a group of intestinal infusion and a group of hepatic portal venous infusion,which respectively received VG by infusion at gastric fundus and duodenum and iv at superior mesenteric vein,and then metabolic rate was calculated by finding out the AUC of VG in the rats’stomachs and intestines. 15 SD rats were divided into a group of intestinal infusion,a group of femoral venous administration and a group of normal saline. At 10 min before administration,the former two groups were given by infusion vera-pamil injection(60 ml/kg),the substrate of CYP3A and P-glycoprotein(P-gp);and the group of normal saline were given by infu-sion of isometric normal saline,and then the rats were given VG as above to observe the effect of verapamil on intestinal absorp-tion of VG. RESULTS:The metabolic rates of VG in the liver,stomach and intestine were 54.9%,1.7% and 91.9% respectively. After infusion of verapamil,slight increase in AUC of VG was found in the rats in the group of intestinal infusion. CONCLU-SIONS:The first-pass effects in the liver and intestine are the main factors related to the low bioavailability of VG. Based on pre-liminary judgment,VG is the substrate of intestinal CYP3A and/or P-gp.

Transdermal drug delivery system: A review.

Delivery of drugs through the skin has been always a challenging area for research due to barrier properties exhibit by the outermost layer of skin stratum corneum. In the last two decades, the transdermal drug delivery system has become a proven technology that offers significant clinical benefits over other dosage forms. Because transdermal drug delivery offers controlled as well as predetermined rate of release of the drug into the patient, it able to maintain steady state blood concentration. It’s a desirable form of drug delivery because of the obvious advantages e.g.convenient and pain-free self-administration for patients, avoidance of hepatic first-pass metabolism and the GI tract for poorly bioavailable drugs over other routes of delivery. The outlook for continued growth of the TDD market is very optimistic.Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. This review emphasizes the three generations of transdermal drug delivery which start a new era of delivery of drug.

A review on intestinal lymphatic drug transport / 中国药学杂志

OBJECTIVE: Available information on the background of the current state and advances of the intestinal lymph trans port of medicines were reviewed. Drug transported by the intestinal lymphatic system can avoid hepatic first-pass metabolism, increase the bioavalibitlty of the highly lipophilic drug, and it is of importance for immunomodulatory, anticancer and anti-infective drugs. METHODS: We conducted a systematic literature review of articles published recent years, analysis and summaries are made upon the advances and methods applied for the increase of the intestinal lymph transport. RESULTS AND CONCLUSION: Intestinal lymphatic transport can increase the bioavailability via a reduction in the first-pass metabolism and the possibility of specifically targeting drugs to regions of the lymphatics, thus it is very advantageous for drugs that are under significant first-pass metabolism. The present review embodies a brief background of the mechanism of access of drugs to the intestinal lymph, a discussion on the links between lipid absorption and transport of highly lipophilic drugs, and approaches for enhancing lymphatic drug transport. Finally, experimental models of the lymphatic transport are also discussed.

Intranasal drug delivery system- A glimpse to become maestro.

Intranasal drug delivery – which has been practiced for thousands of years, has been given a new lease of life. It is a useful delivery method for drugs that are active in low doses and show no minimal oral bioavailability such as proteins and peptides. One of the reasons for the low degree of absorption of peptides and proteins via the nasal route is rapid movement away from the absorption site in the nasal cavity due to the Mucociliary Clearance mechanism. The nasal route circumvents hepatic first pass elimination associated with the oral delivery: it is easily accessible and suitable for self-medication. The large surface area of the nasal mucosa affords a rapid onset of therapeutic effect, potential for direct-to-central nervous system delivery, no first-pass metabolism, and non-invasiveness; all of which may maximize patient convenience, comfort, and compliance. IN delivery is non-invasive, essentially painless, does not require sterile preparation, and is easily and readily administered by the patient or a physician, e.g., in an emergency setting. Furthermore, the nasal route may offer improved delivery for “non-Lipinski” drugs.

Role of intestinal cytochrome P450s in drug metabolism / 中国药科大学学报

The uptake of oral administered drugs primarily occurs in the small intestine,which also has the capability to metabolize drugs.Both phase Ⅰ and phase Ⅱ metabolic enzymes were expressed in the intestinal mucosa,and cytochromes P450(CYP450s) are the principle enzymes attributed to the biotransformation of drugs.CYP3A and CYP2C are the most abundant subfamilies,accounting for approximately 80% and 16% of total CYP450s in the intestine.Compared to the liver,the expression and activity of CYP450 enzymes in the intestine was susceptible to inducers or inhibitors,leading to drug-drug interaction.This article reviews the expression of CYP enzymes in small intestine and the role of the gut wall in CYP-mediated xenobiotic metabolism.Possible drug-drug interactions due to induction or inhibition of CYP enzymes in the small intestine are also addressed.

Severe drowsiness caused by oral administration of low dose opioid in a patient with portal stenosis

<b>Purpose</b>: We report a case with portal vein stenosis that showed unexpected drowsiness induced by oral administration of low dose opioid, suggesting elevation of opioid level in blood. <b>Case report</b>: A 60-year-old woman developed portal vein stenosis caused by postoperative local recurrence and lymph node metastasis after operation of lower bile duct carcinoma. Her doctor administrated 10mg/day of oral controlled-release oxycodone tablet to her and she became drowsy. Therefore, we started powdered form of oral sustained release morphine with 10mg/day and reduced the dose to 5 mg/day; however, her drowsiness persisted. Finally, the symptom was remarkably improved when the administration was changed to a transdermal fentanyl patch (12.5μg/h). <b>Conclusion</b>: Adequate observation is required for cases with reduction in portal blood flow at the time of oral opioid administration. Because oral opioid can escape from first pass effect of the liver and opioid level in blood will be increasing. Furthermore, it is suggested that change in administration method from oral route to percutaneous one may be effective for improvement of adverse effects involving increased opioid-level in blood. Palliat Care Res 2008; 3(2): 331-334

Impact of CYP3A4 and P-glycoprotein on drug disposition in intestine / 中国临床药理学与治疗学

Intestinal CYP3A4-mediated biotransformation and active efflux of absorbed drug by P-glycoprotein are major determinants of bioavailability of orally administered drugs. The expression of CYP3A4 and P-glycoprotein in the intestine is not co-ordinately regulated. However, synergistic actions of CYP3A4 and P-glycoprotein in intestinal drug disposition have been confirmed by in vitro and animal studies. Further understanding of this interaction would be potentially useful to improve oral bioavailability of CYP3A4/P-glycoprotein substrates.