Purpose: The present research work was designed to formulate and evaluate carbamazepine (CBZ) loaded nanostructured lipid carrier (NLC) based in-situ gel for nasal delivery. Methods: The NLC formulation of CBZ was prepared by microemulsion technique followed by probe sonication and evaluated for particle size, zeta potential, entrapment efficiency and in vitro drug diffusion. NLC formulation was incorporated into in-situ gelling formulation using poloxamer 407 (P407), poloxamer 188 (P188) and mucoadhesive polymer. The effect of concentration of poloxamer 188 (X1 ), type of mucoadhesive polymer (X2 ) and concentration of mucoadhesive polymer (X3 ) on gelling temperature (Y1 ) and drug diffusion after 8 h (Y2 ) was studied using Box-Behnken design. In vivo anticonvulsant activity of optimized formulation was studied in Wistar rats by maximal electro-convulsion model (MES). Results: The optimized CBZ NLC formulation, with 20% drug loading, 0.5:1 as Precirol:Capmul MCM ratio as lipid phase and 1:3 as Lipid:Smix ratio, resulted in 89.73±0.2% drug entrapment, 55.95±1.09% of drug diffusion after 8 h, particle size of 132.8 nm with polydispersity index of 0.302 and zeta potential of -29.2±6.1 mV. The in-situ gel formulation with 20% P407, 5% P188 and 0.2% chitosan was optimized and demonstrated excellent gelling ability, gelling temperature in the range of 30 to 35°C, 42.46% of drug diffusion in 8 h by Fickian diffusion mechanism and 31.34±0.76% of drug permeation through sheep nasal mucosa. In vitro anticonvulsant activity in MES model in rat demonstrated significant efficacy (71.95% protection against seizure in extension phase) as compared to plain in-situ nasal gel (50.26% protection against seizure in extension phase). Conclusion: NLC based in-situ gelling formulation demonstrated its potential for nasal delivery of CBZ with improved anticonvulsant activity.

Hot Melt Extrusion (HME) is a continuous pharmaceutical manufacturing process that has been extensively investigated for solubility improvement and taste masking of active pharmaceutical ingredients. Recently, it is being explored for its application in 3D printing. 3D printing of pharmaceuticals allows flexibility of dosage form design, customization of dosage form for personalized therapy and the possibility of complex designs with the inclusion of multiple actives in a single unit dosage form. Fused Deposition Modeling (FDM) is a 3D printing technique with a variety of applications in pharmaceutical dosage form development. FDM process requires a polymer filament as the starting material that can be obtained by hot melt extrusion. Recent reports suggest enormous applications of a combination of hot melt extrusion and FDM technology in 3D printing of pharmaceuticals and need to be investigated further. This review in detail describes the HME process, along with its application in 3D printing. The review also summarizes the published reports on the application of HME coupled with 3D printing technology in drug delivery.

Worldwide, 40 to 50% of women suffer from reproductive tract infections. Most of these infections are mixed infections, are recurrent and difficult to treat with antimicrobials or antifungals alone. For symptomatic relief of infections, oral antimicrobial therapy must be combined with topical therapy. The purpose of this work is to optimize and develop a polyelectrolyte complex (PEC) of chitosan/anion for the formulation of posaconazole- and probiotic-loaded vaginal hydrogel inserts with prolonged release and significant mucoadhesion. PECs were prepared using chitosan as cationic and carrageenan, pectin and polycarbophil as anionic polymers via a lyophilization technique. PEC formation was confirmed by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry, by observing changes in its surface, physical and thermal properties. The probiotic, Lactobacillus casei, was added to the PEC during the lyophilization process and the effect on the probiotic viability was studied. The PECs were further compressed along with posaconazole to form hydrogel inserts and optimized using a 3² full-factorial design. The hydrogel inserts were assessed for swelling behavior, drug release, in vitro mucoadhesion and in vitro antifungal activity. The chitosan–pectin hydrogel insert demonstrated excellent mucoadhesion (1.25 N), sustained drug release (88.2 ± 2.4% in 8 h) and a swelling index of 154.7%. The efficacy of hydrogel inserts was evaluated using in vitro study with a co-culture of Lactobacillus casei and Candida albicans. This study revealed an increase in Lactobacilli casei count and a significant drop in the viable count of Candida albicans (4-log reduction in 24 h), indicating the effectiveness of hydrogel inserts in alleviating the fungal infection. Overall, our study demonstrated the potential of the hydrogel insert for preventing vaginal infection and restoring normal vaginal microbiota.

A systematic design of experiment (DoE) based sensitive, robust high performance thin layer chromatographic (HPTLC) method was established for simultaneous estimation of gallic acid (GA), quercetin (QT), and rutin (RT) from ethanolic and aqueous leaf extracts of Moringa oleifera. The chromatographic separation was carried on Merck TLC aluminum sheets of silica gel 60 F254 (10×10 cm) with mobile phase of toluene: ethyl acetate: methanol: formic acid (4.9:4.1:2:0.5, v/v/v/v) with densitometric scanning at 300 nm. The critical method parameters were initially identified by regular two level factorial design and further systematically optimized using a central composite design, evaluating the effect on selected critical analytical attributes, retention factor (RF), and peak area. The Pareto charts, 3D response surface plots, and polynomial equations for the generated models suggested significant influence of the selected factors on responses of QT, GA, and RT. The desirability and overlay plots employed provided appropriate solutions that were experimentally validated. Under the optimized conditions, the biomarkers were suitably resolved with RF values of 0.64±0.02, 0.80±0.03, and 0.22±0.02 for GA, QT, and RT, respectively, with wide linear dynamic range (200-1200 ng/band each), high accuracy (98.1-99.4%), and intra- and interday precision (%RSD <2%). When employed for quantification of these biomarkers in Moringa oleifera extracts, the ethanolic and aqueous extracts exhibited higher content of QT (993.5 μg/g and 832 μg/g, respectively). The ethanolic extract showed a larger amount of RT (701 μg/g). In contrast, aqueous extract exhibited a higher proportion of GA (591.1 μg/g) compared to ethanolic extract (150 μg/g). This validated HPTLC method developed through a DoE approach was successfully employed for quantification of GA, QT, and RT from Moringa oleifera extracts and may also be extended for their simultaneous estimation in other herbal extracts, thereby reducing time, and may serve as a cost effective tool for analysis.

Introduction: Spherical agglomeration is one of the novel techniques for improvement of flow and dissolution properties of drugs. Cilostazol is a biopharmaceutics classification system Class II drug with poor solubility resulting in limited bioavailability. The present study aims at improving the solubility and dissolution of cilostazol by crystallo-co-agglomeration technique. Materials and Methods: Cilostazol agglomerates were prepared using various polymers with varying concentration of hydroxypropyl methylcellulose E 50 (HPMC E50), polyvinyl pyrrolidone K30 (PVP K30), and polyethylene glycol 6000. The influence of polymer concentration on spherical agglomerate formation was studied by 32 factorial design. Cilostazol agglomerates were evaluated for percent yield, mean particle size, drug content, aqueous solubility, and in vitro dissolution and further characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Results: The agglomeration process resulted in optimized formulation, F3 with mean agglomerate size of 210.0 ± 0.56 μm, excellent flow properties, approximately 15-fold increase in solubility than pure cilostazol and complete drug release in 60 min. Process yield, agglomerate size, and drug release were affected by amount of PVP K 30 and HPMC E50. The presence of drug microcrystal was confirmed by SEM, whereas FTIR study indicated no chemical change. Increase in drug solubility was attributed to change of crystalline drug to amorphous form that is evident in DSC and XRD. Conclusion: Crystallo-co-agglomeration can be adopted as an important approach for increasing the solubility and dissolution of poorly soluble drug.