Characterization, Optimization, In Vitro and In Vivo Evaluation of Simvastatin Proliposomes, as a Drug Delivery.

Simvastatin a cholesterol-lowering agent used to treat hypercholesterolemia, coronary heart disease, and dyslipidemia. However, simvastatin (SV) has shown low oral bioavailability in GIT. The main purpose of the work was to develop proliposomal formulations to increase the oral bioavailability of SV. Film deposition on the carrier method has been used to prepare the proliposomes. The proliposomes were assessed for morphology, particulate size, entrapment efficacy, drug-polymer compatibility, in vitro and in vivo studies. FTIR and DSC results revealed no drug-polymer interaction. SEM and XRD analysis conform; proliposomes are spherical, amorphous in nature, so that it enhances the solubility of SV between 15.01 ± 0.026 and 57.80 ± 0.015 µg/mL in pH 7.4 phosphate buffer. The optimised formulation (PL6) shows drug release up to 12 h (99.78 ± 0.067%). The pharmacokinetics of pure SV and SV proliposomes (SVP) in rats were Tmax 2 ± 0.5 and 4 ± 0.7 h, Cmax 10.4 ± 2.921 and 21.18 ± 12.321 µg/mL, AUC0-∞ 67.124 ± 0.23 and 179.75 ± 1.541 µg/mL h, respectively. Optimised SVP shows a significant improvement in the rate and absorption of SV. The optimised formulation showed enhanced oral bioavailability of SV in Albino Wister rats and offers a new technique to improve the poor water-soluble drug absorption in the gastrointestinal system.

Piperine-Loaded In Situ Gel: Formulation, In Vitro Characterization, and Clinical Evaluation against Periodontitis.

Periodontitis is an inflammatory disorder associated with dysbiosis and characterized by microbiologically related, host-mediated inflammation that leads to the damage of periodontal tissues including gingiva, connective tissues, and alveolar bone. The aim of this study was to develop an in situ gel consisting of piperine. Eight in situ gel formulations were designed by varying the concentration of deacylated gellan gum cross-linked with sodium tripolyphosphate, and poloxamer-407. The prepared gels were evaluated for gelation temperature, gelation time, viscosity, piperine-loading efficiency, and piperine release. Finally, the optimized formula was evaluated for anti-inflammatory effectiveness among human patients during a 14-day follow-up. The optimized in situ gel formulation exhibited a gelation temperature of 35 ± 1 °C, gelling of 36 ± 1 s, excellent syringeability, and piperine loading of 95.3 ± 2.3%. This formulation efficiently sustained in vitro drug release for up to 72 h. In vivo studies revealed an efficient sol-to-gel transformation of optimized in situ gel formulation at physiological conditions, permitting an efficient residence time of the formulation within a periodontitis pocket. Most importantly, a clinical study revealed that treatment with the optimized formulation elicited a significant reduction in the mean plaque score (p = 0.001), gingival index (p = 0.003), and pocket depth (p = 0.002), and exerted a potent anti-inflammatory potential, compared to the control group. Collectively, piperine-loaded in situ gel might represent a viable therapeutic approach for the management of gingival and periodontal diseases.

Modulation of Drug Release from Natural Polymer Matrices by Response Surface Methodology: in vitro and in vivo Evaluation.

PURPOSE: The present work aimed at challenging the efficacy of natural gums, karaya and locust bean gum, as matrix-forming polymers for the formulation of sustained-release tablets of diltiazem, a model drug. METHODS: Central design composite was adopted for the formulation and optimization of tablet formulations. The two gums have been selected as independent variables. The dependent factors chosen were the amount of drug released in 1st hour (Y1), amount of drug released after 12 h (Y2), diffusion exponent (Y3), and time for half of the total drug released (T50%) (Y4). Wet granulation approach was used for the formulation of tablets. FT-IR, DSC, in vitro dissolution, swelling-erosion investigations, SEM, and stability studies were carried out. RESULTS AND DISCUSSION: It was evident that the release pattern from the prepared formulations was significantly influenced by the quantity of gum(s) in the tablet. FT-IR and DSC results confirm drug-polymer compatibility. Polynomial equations were used for the prediction of quantitative impact of independent factors at different levels on response variables. After ANOVA analysis, the significant factors were considered for constrained optimization to get the optimized formula. The optimized formula generated by the response surface methodology was evaluated both for in vitro and in vivo properties. The optimized formula and a sustained-release marketed product were subjected to in vivo studies in rabbits and the results of the t-test demonstrated insignificant variation in pharmacokinetic parameters among the two formulations, confirming that the prepared tablet showed sustained-release profile. CONCLUSION: The results indicated that karaya and locust bean gum can be effectively used to formulate sustained-release tablets.

Development and Optimization of Dual Drugs (Isoniazid and Moxiflox-acin) Loaded Functional PLGA Nanoparticles for the Synergistic Treatment of Tuberculosis.

BACKGROUND: The management of TB is difficult due to the resistance developed by Mycobacterium tuberculosis against anti-tubercular drugs causes the new challenges for treating and managing the disease. OBJECTIVE: The objective of the study was to combat multiple drug resistance (MDR) exhibited by mycobacterium species by synthesizing Dual Drug Conjugate nanoparticle (DDC) using Isoniazid (INH) and Moxifloxacin (MOXI). METHOD: The reaction was nucleophilic substitution using hydrolysable linkers like Chloroacetyl chloride (CAC) & Succinyl chloride (SCL). The drugs were covalently linked as INH-CAC-MOXI (DDC-1) and INH-SCL-MOXI (DDC-2). The DDC-1 & DDC-2 were subjected to hydrolysability tests at different pH solutions. The modified drugs were formulated into Poly (D, L-Lactic-co-Glycolide) nanoparticles using single emulsion technique. Design Expert® (version 8.0.1) software was used for designing, and evaluating the prepared formulation by employing response surface, optimal design of experiment technique. RESULT: The prepared nanoparticles were characterized for compatibility studies using Fourier Transform Infrared Spectroscopy, Nuclear Magnetic Resonance, particle size, size distribution, Zeta potential, drug entrapment efficiency and Scanning Electron Microscopy. Microbiological studies on pure drug and the conjugate indicated better activity of conjugate compared to pure drug alone or 1:1 physical mixture of drug. The nanoparticles were further subjected to drug release studies and accelerated stability studies. CONCLUSION: The present study offers a key to the challenge of loading different types of drugs onto the same drug delivery vehicle with efficient loading capacity, thus enabling better treatment for TB.

Novel interpenetrating polymer matrix network microparticles for intestinal drug delivery.

This paper deals with the synthesis and characterization of Ghatti gum (GG) and chitosan (CS) IPN MP prepared by emulsion-cross-linking method. Glutaraldehyde (GA) was used as a cross-linker. IPN microparticles were used to deliver (DS) Diclofenac sodium (Model anti inflammatory drug) to the intestine. IPN MP were characterized by Scanning electron microscopy (SEM), differential scanning calorimetric (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and evaluated for in vitro dissolution rate. FTIR studies assessed the formation of IPN structure. The surface morphology was studied by SEM. Particle sizes ranged between 294 to 366 µm. After encapsulation into IPN microparticles DSC studies were performed to recognize the crystalline nature of drug. DS percentage encapsulation efficiency (%EE) ranged from 84.09 to 96.81%. Equilibrium swelling was performed in buffer solution (pH 7.4). In-vitro release studies indicated the dependence of drug release rates on both the amount of chitosan and GG used in grounding of microparticles. The release was extended up to 12 hrs and release rates were fitted into an empirical equation to work out the diffusion parameter which indicates a Non-Fickian release. Continuous dissolution-absorption studies were carried out using everted rat intestine for optimized formulation (F9).