Optimization of Self-Double Emulsifying Drug Delivery System Using Design of Experiments for Enhanced Oral Bioavailability of Gentamicin: In-vitro, Ex-vivo and In-vivo Studies.

Water-in-oil-in-water (w/o/w) double emulsions have shown excellent capability in augmenting the enteral bioavailability of BCS class III drugs, besides being effective controlled-release formulations. However, the problem of thermodynamic instability has restrained their industrial applicability. The self-double emulsifying drug delivery system (SDEDDS) is one of several approaches used to improve the stability of double emulsions. SDEDDS is a mixture of primary emulsion and secondary surfactant that can spontaneously emulsify into double emulsions in an external aqueous environment with mild agitation. Here, we prepared SDEDDS of gentamicin sulfate by response surface methodology. Selected optimized formulations (ODS1 and ODS2) were evaluated for zeta potential (Y1), optical clarity (Y2), release at 420 min (Y3), emulsion stability index (Y4) and self-emulsification time (Y5). For ODS1, Y1=-35.45 (±1.06)mV, Y2=53.19 (±0.35)%, Y3=75.79 (±0.60)%, Y4=93.97(±0.15)% and Y5=0.631 (±0.014)min, whereas for ODS2, Y1=-35.70 (±0.56)mV, Y2=48.09 (±0.64)%, Y3=76.61 (±0.99)%, Y4=93.00(±0.94)% and Y5=0.687(±0.02)min. Furthermore, ex-vivo studies on intestinal permeability revealed that SDEDDS improved membrane permeability compared to drug solution. Histopathology investigations revealed that SDEDDS promoted permeation without causing significant local membrane distortion. In addition, in-vivo studies revealed a 2.84 -fold increase in AUC0-∞ of optimized SDEDD compared to pure drug oral solution.

Endodontic Management of Various Canal Morphologies in Maxillary First Molars: A Series of Four Case Reports.

The success of nonsurgical endodontic management depends on the complete elimination of infection that compromises the tooth function. Thorough knowledge about the root canal anatomy is one of the principal factors in achieving a successful outcome. The morphology of root canals is not always typical. Maxillary molars, known for varied morphology, require advanced imaging modalities such as cone-beam computed tomography. This case report describes a series of four maxillary molars with different forms, numbers, and configurations of root canals and with unusual morphology, including a case of a third mesiobuccal canal, a case of a second mesiobuccal canal with two palatal canals (mesiopalatal and distopalatal), a case of three mesiobuccal canals, three distobuccal canals, and two palatal canals (mesiopalatal and distopalatal), and a case of taurodontism, where different access cavity modifications, diagnostic methods, and magnifications were considered.