Sac Technique Research Articles

Possible Role of P-Glycoprotein in Cyclosporine -Acitretin Drug Interaction

P-glycoprotein, an efflux transporter prevents intracellular accumulation of xenobiotics. Cyclosporine A and acitretin are used to treat psoriasis. The present research work aims to investigate the possible role of P-glycoprotein in Cyclosporine- Acitretin drug interaction due to evidence of both drugs having affinity for P-glycoprotein.The study has three different objective namely to assess apparent permeability coefficient of cyclosporine in presence of acitretin by non-everted sac technique, to study the intestinal permeation and absorption kinetics of cyclosporine in presence of acitretin by single pass intestinal perfusion (SPIP) technique and to study the influence of acitretin on oral bioavailability of cyclosporine in Wistar rats.The result of ex vivo, in situ and in vivo study showed that cyclosporine level increased in a time dependent manner. As the dose of acitretin increases the cyclosporine concentration in all three methods tend to increase and was statistically significant. The improvement in absorption of cyclosporine may be due to the inhibition of P-glycoprotein transporter in the intestine by acitretin. Thus acitretin may enhance the oral pharmacokinetics of cyclosporine. Hence this combination may require close monitoring for better therapeutic outcome. Our study confirmed the inhibitory role of acitretin on P-glycoprotein leading to increase concentration of cyclosporine.

Comparison of stent-assisted and no-stent coil embolization for safety and effectiveness in the treatment of ruptured intracranial aneurysms.

The safety of the stent-assisted coil embolization (SAC) technique for acutely ruptured aneurysms has not been established yet. SAC is believed to be associated with a high risk of thromboembolic and hemorrhagic complications in acute subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the safety and efficacy of the SAC technique in the setting of acutely ruptured aneurysm. A total of 102 patients who received endovascular treatment for acute SAH between January 2011 and December 2017 were enrolled. The SAC technique was performed in 38 of these patients, whereas the no-stent coil embolization (NSC) technique was performed in 64. The safety and efficacy of the SAC technique in acute SAH was evaluated as compared with the NSC technique by retrospective analysis of radiological and clinical outcomes. There were no significant differences in clinical or angiographic outcomes between the SAC and NSC techniques in patients with acute SAH. The rate of ventriculostomy-related hemorrhagic complications was higher in the SAC group than that in the NSC group (63.6% vs 12.5%; OR 12.25, 95% CI 1.78-83.94, p = 0.01). However, all these complications were asymptomatic and so small that they were only able to be diagnosed with imaging. Ruptured wide-necked aneurysms could be effectively and safely treated with the SAC technique, which showed clinical and angiographic outcomes similar to those of the NSC technique. Hence, the SAC technique with dual-antiplatelet drugs may be a viable option even in acute SAH.

New sensible method to quantize the intestinal absorption of receptor ligands

In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the everted gut sac technique. The compound chosen for the present study is one of the most potent and selective A3AR agonist reported so far, named AR 170 (N6-methyl-2-phenylethynyl-5′-N-methylcarboxamidoadenosine). In order to evaluate the intestinal absorption of AR 170 the radioligand binding assay in comparison with HPLC-DAD was used. Results showed that the compound is absorbed via passive diffusion by paracellular pathway. The concentrations determined in the serosal (inside the sac) fluid by radioligand binding assay are in good agreement with those obtained through the widely used HPLC/MS protocol, demonstrating the reliability of the method. It is worthwhile to note that the radioligand binding assay allows detecting very low concentrations of analyte, thus offering an excellent tool to measure the intestinal absorption of receptor ligands. Moreover, the AR 170 quantity outside the gut sac and the interaction with A3AR could presuppose good topical anti-inflammatory effects of this compound.

Comparison of calcium absorption from nano- and micro-sized calcium salts using everted gut sac technique

The present study aimed to compare the calcium absorption from calcium carbonate and calcium phosphate in nano and micro-sized forms using everted gut sac technique. It was found that calcium concentrations in sac fluid were higher after incubation in nano-sized calcium carbonate than micro-sized calcium carbonate by 18.23% at 45 min and 21.39% at 75 min. Likewise, Ca concentration in sac fluid was 20.50 and 15.13% higher in nano-sized calcium phosphate than those incubated in micro-sized forms at 45 and 75 min, respectively. Present study revealed that calcium carbonate and calcium phosphate are more extensively absorbed in nano-sized forms than in microsized forms, suggesting their possible use as calcium supplements in poultry and livestock farming.

Retromuscular mesh and hernial sac technique in the reconstruction of 139 cases of large median incisional hernias: one institution's experience.

Incisional hernia is the most common complication of laparotomy. Postoperative parietal defects tend to relapse, even after the most optimal surgical methods. The aim of this study was to present the effectiveness of an adapted retromuscular technique with prolene mesh and a hernial sac, in patients with large incisional median hernias. The reported results were obtained by our team after more than 15years of experience. This retrospective study included 139 consecutive cases of large median incisional hernias operated on using a retromuscular mesh and hernial sac technique. The cross-sectional diameter of incisional hernias was larger than 10cm, being classified in the W3 group, according to the European Hernia Society classification. The study included 83 females (59.71%) and 56 males (40.29%) with a median age of 62.4 ± 16.6years and an average body mass index of 32.4 ± 7.6 kg. The hernia was supraumbilically located in 54 cases, subumbilically in 61 cases, and supra- and subumbilically in 24 cases. Postoperative complications were recorded in eight cases (5.75%): one case with a hematoma in the right abdominal muscle sheath; five cases with supra-aponeurotic seromas; two cases with skin necrosis and one with a mesh infection. Recurrence occurred in seven cases (5.03%): four cases in the first 2 years postoperatively and three cases in the third year after surgery. The retromuscular technique with prolene mesh and a hernial sac is an effective method of restoring the integrity of the abdominal wall in large median incisional hernias with low rates of morbidity and recurrence.

Nonligation and ligation of hernial sac technique during orchiopexy for palpable undescended testis in children: A comparative study

Purpose: We prospectively evaluated the surgical outcomes of non ligation of hernial sac technique in children with a palpable undescended testis compared with the traditional hernial sac ligation technique during orchiopexy.
 Material and Methods: A total of 34 orchiopexies (30 children with age ranged from 6 months to 5 years) were included and randomly assigned to the non ligation of hernial sac technique orchiopexy group (Group-A, 15 children, 16 testes) and the traditional hernial sac ligation orchiopexy group (Group-B, 15 children, 18 testes). Operation time and surgical complications were compared between the two groups. Complications, testicular location and development of inguinal hernia were assessed at the follow-up evaluation for 6 months postoperatively.
 Results: The operation time was significantly shorter in Group-A (34.13±10.3 minutes) than Group-B (73.73±28.97 minutes) (<p001). Postoperative complications were found in two cases (wound infection and testicular re-ascent) in Group-B. Wound infection was managed by conservative care and redo surgery was done for testicular re-ascent after 6 months of operation. None of the patients developed post operative inguinal hernia.
 Conclusion: We conclude that non ligation of hernial sac technique is a simple procedure that is associated with a shorter operation time than the conventional hernial sac ligation technique during open orchiopexy for palpable undescended testis.
 Journal of Paediatric Surgeons of Bangladesh (2016) Vol. 7 (2): 35-40

Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, in vitro Dispersion, Digestion and ex vivo Gut Permeation Studies.

Background: The choice of lipid excipients and their origin are crucial determinant factors in the design of self-nanoemulsifying drug delivery system (SNEDDS).Aim: To investigate the aspects of alternative excipients which can influence the development of efficient SNEDDS and determine the fate of fenofibrate in aqueous media.Methods: SNEDDS of two groups (a and b) were developed using Cremercoor MCT/Capmul MCM and Kollisolv MCT/Imwitor 742 blended oils and water soluble surfactants (to improve lipid polarity) for the model anti-cholesterol drug fenofibrate. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEDDS. Further SNEDDS optimizations were done on the basis of maximum drug loading by equilibrium solubility studies and maximum solubilized drug upon aqueous dispersion by dynamic dispersion studies. In vitro lipolysis was examined under simulated Fed and Fasted conditions. Intestinal permeability study of the optimal SNEDDS formulation was compared with the raw fenofibrate dispersion using non- everted “intestinal sac technique.”Results: Initial characterization and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 (group b) containing formulations generated highly efficient SNEDDS as they are stable and produced lower nanodroplets with higher drug loading (group b) as compared to mixed glycerides of Cremercoor MCT/Capmul MCM (group a). In vitro dispersion and digestion studies confirmed that SNEDDS of group b (polar mixed glycerides) can retain high amount of drug (99% drug in solution for more than 24 h time) in dispersion media and have high recovery after digestion. The results from the permeability assessment confirmed that fenofibrate had 4.3-fold increase with F3b SNEDDS compared with the control.Conclusion: SNEDDS formulations containing alternative excipients (Kollisolv MCT/Imwitor 742 blend) could be a potential oral pharmaceutical product in taking anti-hyperlipidaemic agent fenofibrate to the systemic circulation as solubilized form.

One-stage Stent-assisted Coil Embolization for Rupture-side-unknown Bilateral Vertebral Artery Dissecting Aneurysms in an Acute Stage: A Case Report

Bilateral vertebral artery dissecting aneurysms (VADAs) with subarachnoid hemorrhage (SAH) are rare and their management is still challenging. In this report, we successfully performed one-stage stent-assisted coil embolization (SAC) for bilateral VADAs with SAH in an acute stage, because the ruptured side could not be diagnosed. A 47-year-old woman presented with a sudden onset of headache without laterality, and left-side dominant SAH with bilateral VADAs was noted on computed tomography (CT) scans. The size of aneurysmal dome and neck was similar between the two VADAs, and a bleb was observed only on the right VADA. In computational fluid dynamics (CFD) simulations, findings of wall shear stress (WSS), normalized WSS, and WSS gradient suggested that the left VADA was ruptured, while the oscillatory shear index and aneurysm formation indicator suggested the opposite-side one to be ruptured. Thus, we could not determine which VADA was ruptured by clinical data and CFD analyses. Therefore, we performed simultaneous treatment for the bilateral VADAs by using SAC technique 8 h after the onset under dual antiplatelet and anticoagulation therapies. There was no evidence of rebleeding and stent thrombosis. Stent thrombosis was monitored by duplex color-coded ultrasonography after the intervention. She was discharged without neurological deficits, and 6-month follow-up cerebral angiography demonstrated no recanalization of VADAs. This is the first report showing bilateral VADAs with SAH treated by one-stage SAC within 24 h of SAH, and the potential risks are discussed.

Studies on absorption of nutrients using intestinal sacs of rats fed on different diets

Absorption of glucose, sucrose, glutamic acid and methionine was studied using the intestinal everted sac technique. Rats were fed with potato tubers of Kufri Ashoka, Kufri Chipsona-1 and Kufri Chipsona-2 in combination with casein in 1:1 ratio and casein as a control at eight per cent, protein level. Absorption of sucrose, glucose, glutamic acid and methionine was monitored spectrophotometrically and of glucose, sucrose and glutamic acid by 14C radio assay using scintillation counting. In general, glutamic acid showed higher absorption values than glucose, sucrose and methionine by both the techniques. Rats fed on casein diet exhibited maximum absorption of glutamic acid and methionine. Incorporation of 10 ?mole of lithium decreased considerably the absorption of glucose, sucrose, glutamic acid and methionine. Absorption of nutrients differed between casein and casein-potato tubers diets.

Oral microemulsion of phytoconstituent found in licorice as chemopreventive against benzo(a)pyrene induced forestomach tumors in experimental mice model

Dibenzoylmethane (DBM), a minor phytoconstituent found in roots of licorice (Glycyrhiza glabra) has been reported to exhibit antioxidant and chemopreventive effects. It suffers from a problem of poor aqueous solubility and permeability leading to low oral bioavailability. Microemulsion, a novel colloidal carrier was proposed to improve its solubility in order to achieve enhanced oral biodistribution and efficacy. The microemulsion was prepared using peppermint oil and Tween 20 as oil phase and surfactant respectively. The spherical globules of microemulsion depicted a mean globule size of 157 nm and polydispersity index (PDI) of 0.715. The results of exvivo intestinal permeation using non everted intestinal sac technique demonstrated 5.7 time enhancement in intestinal permeability from microemulsion. During the invivo chemopreventive evaluations using benzo(a)pyrene [B(a)P] induced forestomach tumors in mice model, the treatment with DBM microemulsion, resulted in almost 100% reduction in tumor incidence after the last dose of B(a)P. The histopathological studies suggested the regression of stomach tumors after treatment with DBM microemulsion. Also, the biochemical estimations for oxidative stress markers depicted its improved efficacy in chemoprevention. The above results suggested that oral microemulsion formulation augmented the permeability and effectiveness of DBM as potential chemopreventive agent.

Development of novel amisulpride-loaded liquid self-nanoemulsifying drug delivery systems via dual tackling of its solubility and intestinal permeability

Objective: The aim of the current investigation was at enhancing the oral biopharmaceutical behavior; solubility and intestinal permeability of amisulpride (AMS) via development of liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) containing bioenhancing excipients.Methods: The components of L-SNEDDS were identified via solubility studies and emulsification efficiency tests, and ternary phase diagrams were constructed to identify the efficient self-emulsification regions. The formulated systems were assessed for their thermodynamic stability, globule size, self-emulsification time, optical clarity and in vitro drug release. Ex vivo evaluation using non-everted gut sac technique was adopted for uncovering the permeability enhancing effect of the formulated systems.Results: The optimum formulations were composed of different ratios of Capryol™ 90 as an oil phase, Cremophor® RH40 as a surfactant, and Transcutol® HP as a co-surfactant. All tested formulations were thermodynamically stable with globule sizes ranging from 13.74 to 29.19 nm and emulsification time not exceeding 1 min, indicating the formation of homogenous stable nanoemulsions. In vitro drug release showed significant enhancement from L-SNEDDS formulations compared to aqueous drug suspension. Optimized L-SNEDDS showed significantly higher intestinal permeation compared to plain drug solution with nearly 1.6–2.9 folds increase in the apparent permeability coefficient as demonstrated by the ex vivo studies.Conclusions: The present study proved that AMS could be successfully incorporated into L-SNEDDS for improved dissolution and intestinal permeation leading to enhanced oral delivery.

A Multi-layered Particulate System for Desvenlafaxine Succinate Oral Customized Release

With its reported side effects Desvenlafaxine succinate (DSV) is a good candidate to prepare prolonged release system. Such prolonged release could decrease the rapid DSV absorption after oral administration and reduce its exaggerated side effects. A prolonged release Desvenlafaxine succinate (DSV) multilayered system was prepared by ionotropic gelation using sodium alginate (SA) and calcium chloride as a cross-linker. DSV was incorporated simultaneously during the gelation stage and the formed beads were evaluated for shape and particle size. Thirteen formulation variables including pH, DSV: polymer ratio, cross-linker concentration and curing time were optimized for optimal drug entrapment. The optimized formula was evaluated ex vivo using the everted sac technique to predict DSV absorption through intestinal mucosal cells, follow the permeation and calculate its apparent permeability coefficient. The optimum formulation variables were: pH (8-9), DSV: SA ratio (2:1), cross-linker concentration (5%w/v) and 30 min curing time. Multilayered beads coating using chitosan and SA was compared with uncoated beads or the innovator for DSV release. Coating of the beads greatly retarded DSV release with a release profile similar to that of the innovator. An optimized formula (T13) coated with 0.04% w/v of each of chitosan and SA was selected. The developed system gave rise to a prolonged release pattern with high similarity factor with the innovator. The results of the current work can be applied to prepare controlled release systems of similar drugs that have intense side effects associated with their initial burst after oral administration.

The effect of administration of silver nanoparticles to broiler chickens on estimated intestinal absorption of iron, calcium, and potassium

We postulate that Ag accumulated in the intestines may block ion channels or bind with transport proteins responsible for absorption of mineral elements. The objective of the study was to determine whether and to what degree administration of Ag nanoparticles to broiler chickens affects accumulation of Ag in the intestines. An additional objective of the study was to test whether nanosilver affects absorption of Fe, Ca, and K. The experiment was conducted with 126 broiler chickens assigned to 7 treatments with 3 pens per treatment and 6 broiler chickens per pen. The control treatment did not receive Ag nanoparticles. Broiler chickens received Ag nanoparticles (0.5, 1.0, or 1.5mg/kg body weight/d) via a tube into the crop in three 3-d periods (d 8–10, 22–24, and 36–38) or three 7-d periods (d 8–14, 22–28, and 36–42). After the rearing period (d 42), 6 broiler chickens from each experimental treatment (2 broiler chicken from each pen) with body weight similar to the treatment average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. The study showed that nanosilver supplied via ingestion leads to dose-dependent accumulation of Ag in the intestinal walls. Silver present in the intestines did not interfere with absorption of Ca, but reduced absorption of K and Fe. This was a pilot study and therefore, the research must be continued to definitively verify the results.

A Novel Technique to Detect Code for SAC-OCDMA System

Abstract The main task of optical code division multiple access (OCDMA) system is the detection of code used by a user in presence of multiple access interference (MAI). In this paper, new method of detection known as XOR subtraction detection for spectral amplitude coding OCDMA (SAC-OCDMA) based on double weight codes has been proposed and presented. As MAI is the main source of performance deterioration in OCDMA system, therefore, SAC technique is used in this paper to eliminate the effect of MAI up to a large extent. A comparative analysis is then made between the proposed scheme and other conventional detection schemes used like complimentary subtraction detection, AND subtraction detection and NAND subtraction detection. The system performance is characterized by Q-factor, BER and received optical power (ROP) with respect to input laser power and fiber length. The theoretical and simulation investigations reveal that the proposed detection technique provides better quality factor, security and received power in comparison to other conventional techniques. The wide opening of eye in case of proposed technique also proves its robustness.

Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

Purpose: Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Methods: Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and in vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp) were performed using everted sac technique. Results: Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4h and the highest similarity factor with the innovator (84.7). Conclusion: A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

Relationship between Widening and Position of the Tunnels and Clinical Results of Anterior Cruciate Ligament Reconstruction to Knee Osteoarthritis: 30 Patients at a Minimum Follow-Up of 10 Years

To evaluate the relationship between tunnel position and widening and long-term clinical results in anterior cruciate ligament (ACL) reconstruction, a retrospective cohort of 30 patients undergoing ACL reconstruction with double semitendinous plus double gracilis (SAC technique) with longer than 10-year follow-up was selected. CT scans in the first 3 months and at final follow-up was evaluated. Position, angle, and widening of tunnels including Nebelung criteria were recorded in all CT scans. Physical, KT-1000, and clinical evaluation were performed at final follow-up. Outcomes and knee arthritis severity were evaluated at final follow-up. Mean follow-up was 11.2 ± 1.2. At final follow-up, 85 and 57% of tibial and femoral tunnels, respectively, developed some degree of enlargement. Frontal tibial angle (mean) was 72°, sagittal tibial angle 63°, frontal femoral angle 47°, sagittal femoral angle 20°, and tunnels divergence angle 36°. Preoperatively, KT-1000 30L and Lachman test scores were 5.52 and 5.79 respectively. In the last follow-up, 30L and manual Lachman test scores were 0.97 and 1.13, respectively (p < 0.001). In IKDC scale, pivot shift and Jerk tests showed 83 and 84% grade A results, respectively (p < 0.0001). In Fairbank scale, 23% worsened one grade and 27% worsened more than one grade (p < 0.005). Tibial tunnels widened more than femoral tunnels and further dilatation was found between intermediate and final follow-up. Higher incidence of tibial tunnel widening was observed in patients with tunnel verticalization. Tibial tunnel dilation was associated with long-term degenerative changes but not with final knee instability.

The effect of administration of copper nanoparticles to chickens in drinking water on estimated intestinal absorption of iron, zinc, and calcium

Copper nanoparticles used as a dietary supplement for poultry could affect the absorption of mineral elements. Hence the aim of the study was to determine the effect of administration of copper nanoparticles to chickens in drinking water on intestinal absorption of iron, zinc, and calcium. The experiment was carried out on 126 chicks assigned to seven experimental groups of 18 birds each (3 replications of 6 individuals each). The control group (G-C) did not receive copper nanoparticles. Groups: Cu-5(7), Cu-10(7), and Cu-15(7) received gold nanoparticles in their drinking water in the amounts of 5mg/L for group Cu-5(7), 10mg/L for group Cu-10(7), and 15mg/L for group Cu-15(7) during 8 to 14, 22 to 28, and 36 of 42 days of the life of the chicks. The birds in groups Cu-5(3), Cu-10(3), and Cu-15(3) received copper nanoparticles in the same amounts, but only during 8 to 10, 22 to 24, and 36 to 38 days of life. Blood for analysis was collected from the wing vein of all chicks at the age of 42 days. After the rearing period (day 42), six birds from each experimental group with body weight similar to the group average were slaughtered. The carcasses were dissected and samples of the jejunum were collected for analysis of absorption of selected minerals. Mineral absorption was tested using the in vitro gastrointestinal sac technique. Oral administration of copper nanoparticles to chickens in the amount of 5, 10, and 15mg/L led to accumulation of this element in the intestinal walls. The highest level of copper nanoparticles applied increased Cu content in the blood plasma of the birds. The in vitro study suggests that copper accumulated in the intestines reduces absorption of calcium and zinc, but does not affect iron absorption.

Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal permeation

Genistein (GEN), a potent anticancer agent, suffers from scanty oral bioavailability due to poor solubility and extensive metabolism. This work endeavored to enhance GEN solubility and intestinal permeability via fabrication of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive surfactants. Moreover, the potential of surfactant-free SEPP to address GEN obstacles was investigated. SEPPs were prepared from Phosal® 53MCT, oil/phosphatidylcholine mixture, alone or with only 30% of different surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed globule size analysis, zeta potential (ZP), transmission electron microscopy, and in-vitro release. Ex-vivo intestinal permeation study was performed using non-everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily dispersed with spherical globules within a nano-range size (from 165±15 to 425±20nm) and adequate negative ZP (>−30mV). SEPPs demonstrated a significant enhancement in GEN release compared to drug suspension without superior effect due to added S/CO. Permeation study revealed that at least 12.13% free GEN was permeated after 120min from SEPPs compared to only 3.7% from drug suspension. Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising nanocarrier that enhances GEN bioavailability via improving dissolution and inhibition of pre-systemic clearance.

Brinzolamide-Loaded Nanoemulsions: In vitro Release Evaluation

The aim of this investigation was to design and develop nanoemulsions (NEs) as novel ophthalmic delivery systems for brinzolamide (BZD). Phase behavior of quaternary systems composed of triacetin and CapryolTM 90 (selected oils, screened through the solubility studies), various surfactants (namely, Cremophor RH 40, Brij 35, Labrasol and tyloxapol), Transcutol P (as co-surfactant) and water at different surfactant/co-surfactant weight ratios (Rsm) was investigated by the construction of phase diagrams. Formulations were taken from the o/w NE region on the phase diagrams, depending upon the extent of NE domain. The spontaneous emulsification method was used to prepare various formulations containing 0.4 wt% of the drug. The nanosized character of NEs were evaluated, the cumulative drug release and from the selected formulations was determined for a period of 6 h, using a dialysis sac technique and the release efficiency for NEs was calculated. The therapeutic efficacy of the selected BZD-loaded NEs to lower the IOP was assessed by the calculation of various pharmacodynamic parameters (ie., Emax, Tmax AUC0-6h). In all cases, the average size of the droplets was found to be less than 40 nm. In vitro release studies indicated that the release efficiency in most of the NEs was higher as compared to BZD ophthalmic formulation. Comparison of the pharmacodynamics parameters confirmed the equivalent efficacy of most BZD formulations. It was concluded that NE systems could improve availability of BZD in ocular tissue.

Acyclovir Entrapped N-Trimethyl Chitosan Nanoparticles for Oral Bioavailability Enhancement

Objective: The aim of the study was to evaluate a nanoparticulate system composed of Ntrimethyl chitosan (TMC) for improving the oral bioavailability of Acyclovir (ACV). Methods: TMC was prepared by methylation of chitosan and characterized by H-NMR spectroscopy. The ionic gelation method was used to prepare ACV loaded TMC nanoparticles. Non-everted sac technique was used to assess ex vivo permeation in rats. A pharmacokinetic study of the optimized formulation was carried out in male Wistar rats in comparison with ACV alone. Results: Ex vivo studies exhibited a significant rise in the permeation of ACV from the rat intestinal membrane when formulated as nanoparticles. The results showed an increase in plasma concentration of ACV from the nanoformulation and significant difference (p < 0.05) in pharmacokinetic parameters as compared to pure drug, ACV. Conclusion: The results suggest that higher oral delivery of ACV can be achieved by combining the benefits of both TMC and nanoparticles.