Objective: The study aimed to develop fast-dissolving films (FDFs) of the immunosuppressant drug tacrolimus monohydrate for sublingual administration, employing central composite design (CCD), to improve its bioavailability. Methods: Tacrolimus: β-cyclodextrin inclusion complexes prepared earlier were formulated into FDFs. CCD was used for developing optimal film formulation with the desired characteristics. The solvent casting method was used for the preparation of films. For optimization, the independent variables selected were the concentration of hydroxy propyl methyl cellulose E5 (HPMC E5) (X1) and concentration of croscarmellose sodium (CCS) (X2) and the responses were disintegration time (Y1) and percentage drug release at 5 min (Y2). The suggested optimal films were subjected to further characterization. Results: All the formulations showed good mechanical properties. The composition of optimized FDF constituted 3.016% w/v of HPMC and 11.731%w/w of CCS and its average disintegration time was 27.28s and showed 83.13% mean drug release at 5 min. Differential Scanning calorimetry (DSC) analysis showed complete dispersion and partial conversion into the amorphous form of the drug, which was also confirmed by X-ray diffraction (XRD) studies. Scanning Electron Microscopy (SEM) revealed the smooth and porous nature of the film. Conclusion: The developed FDF may be used sublingually for delivering tacrolimus efficiently, avoiding its oral bioavailability problems.

Objective: Sustained release systems have the potential to enhance the therapeutic responses in the long-term management of psychiatric disorders. In the present study, cross-linked microspheres of the antipsychotic drug Trifluoperazine (TFP) were prepared using biodegradable polymer-chitosan and various in vitro evaluations were performed on the prepared microspheres. Methods: The spray drying technique was used to prepare TFP-loaded chitosan microspheres. Tripolyphosphate (TPP) was incorporated into the chitosan solutions as a cross-linking agent in varying concentrations. Different evaluations like production yield, encapsulation efficiency, drug-polymer compatibility, Scanning Electron Microscopy (SEM), X-ray diffraction studies (XRD), Differential Scanning Colorimetry (DSC), particle size, zeta potential analysis and in vitro drug release studies were performed on the developed formulations. Results: The formulated microparticles exhibited production yields ranging from 38.51 to 57.21% and had reasonably good encapsulation efficiencies (54.52-78.35%). The drug excipient compatibility was confirmed by Infrared Spectroscopy. All the microspheres showed positive zeta potential with a mean diameter ranging from 1.45-3.61µ. SEM images revealed the formation of spherical particles with indentations on the surface. XRD and DSC studies confirmed the presence of an amorphous form of the drug inside the microspheres. The in vitro release profile of TFP from cross-linked chitosan microspheres was influenced considerably by changing the concentration of polymer and crosslinking agent in the formulation. The drug release from (0.5%) chitosan microspheres reduced from 91% to 79%, when TPP concentration was increased from 10% w/w to 30% w/w. All the formulations clearly showed a burst release of the drug in the initial hours and a subsequent sustained release profile. Conclusion: The results of this study suggest that TPP crosslinked spray-dried chitosan microparticles could be a promising method for developing a long-acting drug delivery system intended to effectively treat schizophrenia.

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism.

Objective: The purpose of the present study was to formulate and evaluate the polymeric transdermal delivery system of antipsychotic drug Trifluoperazine (TFP) for sustained drug release. Methods: A transdermal patch loaded with (TFP) was formulated by solvent casting technique. Polyvinyl pyrrolidone (PVP) K-30 and ethyl cellulose (EC) was used as a polymeric matrix with different ratios. Di n-butyl phthalate was used as a plasticizer. The parameters such as thickness, folding endurance and weight variation of the prepared patches were studied. The interaction study by attenuated total reflectance-infrared (ATR-IR) spectroscopy, X-ray diffraction and thermal analysis by differential scanning calorimetry (DSC) were performed. In vitro drug release study was performed by modified paddle over-disc technique. Results: The infrared spectroscopic study confirmed the absence of any chemical interaction between TFP and selected polymers. All the prepared formulations showed folding endurance values ranging from 130-162 and a satisfactory drug loading of 90-95%. In in vitro drug release study, formulations PE-3 and PE-4 exhibited a sustained and stable cumulative release of 54 % and 48% respectively, at the end of 24 h. The DSC and XRD analysis proved the partial conversion of the drug from crystalline to amorphous form when integrated into the polymeric matrix. Conclusion: The prepared transdermal formulations using polymers PVP and ethyl cellulose demonstrated their ability to sustain the release of TFP. The developed formulation could be exploited for multiday therapy of TFP for the effective treatment of schizophrenia with a simplified dosing regimen and enhanced patient compliance.