3D Patient-Specific Biomechanical Model of the Tongue for the Management of Tongue Tumors: Conceptualization to Reality.

Objectives: Increasing use of tobacco by the younger generation has resulted in an increase in oral cavity tumors. Surgical treatment is radical and results in severe functional morbidity. Using computer-aided designing technology, surgical and rehabilitative planning can be better. We present here our concept of a patient-specific biomechanical 3D model of the tongue and its clinical utility in the management of tongue tumors. Methods: Using fused deposition modeling, the 3D model of the tongue was printed which easily differentiates the tumor and the uninvolved tongue by printing in two different colors. The 3D tongue model was used by the surgical and rehabilitation teams to frame the treatment and plan the rehabilitation taking into account the patient preferences and needs. The model was used in two patients with operable squamous cell carcinoma (SCC) of the tongue, and the utility of the model in margin planning, surgical defect assessment, and its aid in the reconstruction and rehabilitation was assessed. Results: Two patients with Stage III SCC of the tongue underwent the surgery based on the plan evolved from the 3D model. All the surgical margins assessed by the frozen section analysis were clear. The model helped in addressing the discordance between patient expectations and surgical outcomes. We found that the model aided the reconstructive surgeon in planning the flap harvest based on the pre-operative defect assessment, which, in turn, translated into better rehabilitative outcomes. Conclusion: 3D biomechanical tongue model is a novel concept and aids in improving the overall treatment outcomes. The realistic 3D reconstructed image model helps the oncologist in planning the resection, enables the reconstructive surgery to more precisely predict the defect volume, and lastly the rehabilitative team in developing better rehabilitation strategies.

Experimental design approach for development of novel microemulsion system and immediate release self microemulsifying tablet of nebivolol HCl

The objective of this study was to determine specific combination of pharmaceutical excipients that lead to formulation of efficient nebivolol hydrochloride SMEDDS and its subsequent formulation into IR-SET (Immediate release- Self emulsifying tablet) which will enhance its solubility and dissolution. Solubility and Pseudo-ternary phase studies were carried out to identify the excipients showing highest solubility and to identify the zone of microemulsion with selected ingredients. Liquid-SMEDDS (L-SMEDDS) were optimized for Concentration of oil(X1) and Smix(X2) and formulated using a combination of Kollisolv GTA as oil, Tween 80 as surfactant and propylene glycol as co-surfactant which gave smaller droplet size(Y1) 55.98nm , Emulsification time (Y2) 16±1.5 s,% transmittance (Y3) 99.94±0.47%. Neusilin US2 was used as solid carrier for solidification of L-SMEDDS in to Solid-SMEDDS (S-SMEDDS) by adsorption technique. IR-SET of nebivolol were formulated with S-SMEDDS and optimized for the concentration of binder (X1) (PVP K30) and superdisintegrant (X2) (KOLLIDON CL) which showed low Disintegration time (Y1) (92±0.5s) and low Friability(Y2)(0.424±0.03%). Also the DSC and XRD data revealed the molecular state of the drug in S-SMEDDS. The extent of in-vivo drug release and ex-vivo diffusion values from L-SMEDDS and IR-SET was much higher than pure drug and marketed tablet. In conclusion, the results showed potential of SMEDDS to improve solubility and thus the bioavailability.

Tracheoesophageal puncture site closure with sternocleidomastoid musculocutaneous transposition flap.

INTRODUCTION: Tracheoesophageal voice prosthesis is highly effective in providing speech after total laryngectomy. Although it is a safe method, in certain cases dilatation or leakage occurs around the prosthesis that needs closure of tracheoesophageal fistula. Both non-surgical and surgical methods for closure have been described. Surgical methods are used when non-surgical methods fail. We present the use of the sternocleidomastoid musculocutaneous (SCMMC) transposition flap for the closure of tracheoesophageal fistula. MATERIALS AND METHODS: An incision is made at the mucocutaneous junction circumferentially around the tracheostoma. Tracheoesophageal space is dissected down to and beyond the fistula. The tracheoesophageal tract is divided. The oesophageal mucosa is closed with simple sutures. Then SCMMC transposition flap is raised and transposed to cover sutured oesophagus and the defect between the oesophagus and the trachea. RESULTS: This study was done prospectively over a period of 1 year from June 2012 to May 2013. This technique was used in patients with pliable neck skin. In nine patients, this procedure was done (inferior based flap in nine cases) and it was successful in eight patients. In one case, there was dehiscence at the leading edge of flap with oesophageal dehiscence, which required a second procedure. In two cases, there was marginal necrosis of flap, which healed without any intervention. Nine patients in this series were post-radiation. CONCLUSION: This method of closure is simple and effective for patients with pliable neck skin, who require permanent closure of the tracheoesophageal fistula.

Enhanced transdermal delivery of granisetron by using iontophoresis.

The purpose of the present study was to explore the passive and electrically assisted transdermal transport of Granisetron hydrochloride (GRA) in solution and gel formulation through iontophoresis and also the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting. In this study, iontophoretic permeation of GRA through guinea pig skin using silver-silver chloride electrode was performed and the effects of different variables on this phenomenon were evaluated. Preliminary in-vitro studies using aqueous GRA formulations investigating the effect of drug concentration (5, 10, 15 and 20 mg mL(-1)) on passive permeation, current density (0.2, 0.4 and 0.5 mA cm(-2)), mode of current application, penetration enhancers and effect of application duration were performed. As expected, GRA delivery was found to be increased with the elevation in drug concentration and current density. Anodal continuous current delivery was more effective in the permeation of GRA than the pulsed current method. Penetration enhancers were ineffective to show synergistic effect in conjunction with iontophoresis. It was evident that reservoir in the skin was not formed during the iontophoretic delivery. The results confirm that GRA is an excellent candidate for iontophoresis. The present study demonstrated the feasibility of GRA transdermal transport through the Lutrol F-127 gel by iontophoresis. Further in-vivo studies will be required to support in-vitro conclusions and develop in-vitro, in-vivo correlations.

Transdermal iontophoretic delivery of timolol maleate

Transdermal iontophoresis would be a promising method for the systemic delivery of water soluble and ionic drugs of relatively high molecular size, including peptides. The objective of the present study was to investigate the effect of biological variable such as guinea pig and human cadaver skin and other variables like drug concentration, current density on the transdermal iontophoretic transport of timolol maleate. The permeation profile of drug using solution and gel formulation was studied and compared. For better bioavailability, better patient compliance, and enhanced delivery, an iontophoretic drug delivery system of a timolol maleate matrix gel was formulated using Carbopol 974P. The study was conducted using silver-silver chloride electrodes across the guinea pig and human cadaver skin. Viscosity measurements and flux calculations indicated the suitability of the Carbopol 974P gel for transdermal iontophoretic delivery of timolol maleate. Anodal iontophoresis with silver-silver chloride electrode significantly increased the timolol maleate skin permeation as compared with the passive permeation study. The amount of timolol maleate transported during iontophoresis was significantly different among the different skins. However, iontophoretic gel formulations provided required flux of drug through human cadaver skin.

A iontoforese transdérmica seria um método promissor para a liberação sistêmica de fármacos solúveis em água e iônicos de relativamente elevado tamanho molecular, incluindo peptídeos. O objetivo do presente estudo foi investigar o efeito da variável biológica, tais como cobaia e pele de cadáver humano, e outras variáveis como concentração do fármaco, densidade de corrente sobre o transporte transdérmico iontoforético de maleato de timolol. Comparou-se o perfil de permeação do fármaco usando a formulação de solução e de gel. Para melhor biodisponibilidade, melhor adesão do paciente e liberação aprimorada, formulou-se sistema de liberação iontoforética gel de maleato de timolol usando Carbopol 974P. O estudo foi conduzido usando eletrodos de prata-cloreto de prata na cobaia e na pele de cadáver humano. Medidas de viscosidade e de fluxo indicaram a adequação do gel Carbopol 974 P para liberação iontoforética transdérmica do maleato de timolol. A iontoforese anódica com eletrodo de prata-cloreto de prata aumentou significativamente a permeação dérmica do maleato de timolol, comparativamente à permeação passiva. A quantidade de maleato de timolol transportado durante a iontoforese foi significativamente diferente entre as diferentes peles . No entanto, as formulações iontoforéticas de gel forneceram o fluxo necessário do fármaco através da pele de cadáver humano.

Rabeprazole sodium delayed-release multiparticulates: Effect of enteric coating layers on product performance.

Rabeprazole sodium is one of the most effective proton pump inhibitors (PPIs) used in antiulcer therapy. Like most other PPIs, owing to its acid-labile nature, the drug is formulated as enteric-coated dosage form. Conventional means of producing delayed release multiparticulate dosage forms of PPIs require large quantities of enteric polymer coatings. In the present study, in order to better evaluate the effect of polymeric coating on product performance, the pellet core structure and composition was kept constant. Four different enteric-coating formulations and designs were evaluated. Enteric-coated drug multiparticulates prepared with single polymeric coatings (acrylic or cellulosic) were compared with two different polymeric layer coatings to evaluate the effectiveness of latter coatings in more effectively producing a better rabeprazole sodium delayed-release pellet product. The pH-dependent, enteric acrylic, and cellulosic polymers were used either alone, in combination, or applied one over the other to impart delayed-release properties to the core drug pellets. It was demonstrated that dual delayed-release coating with two different enteric polymers-an inner acrylic coating followed by an outer cellulosic coating-yields the best product that provides all the desired physicochemical and drug dissolution characteristics.