Curcumin loaded chitosan nanoparticles impregnated into collagen-alginate scaffolds for diabetic wound healing.

Diabetic wounds are a common complication in patients with diabetes that often lead to amputation. Although the pathophysiology of diabetic wound is multifactorial, chronic inflammation and lack of tissue regeneration leads to impair wound healing in diabetes. Application of curcumin (CUR) which is a well-known anti-inflammatory and antioxidant agent could be better strategy in diabetic wound healing. However, low bioavailability and poor stability of CUR hinders its application. Hence, in present study a novel nanohybrid scaffold has been prepared by incorporating CUR in chitosan nanoparticles (CSNPs) to improve stability and solubility followed by impregnation of prepared CUR-CSNPs into collagen scaffold (nanohybrid scaffold) for better tissue regeneration application. The prepared CUR-CSNPs were evaluated for particle size, zeta potential, SEM, differential scanning calorimetry and X-ray powder diffraction studies and the novel nanohybrid is evaluated for morphology, biodegradability, biocompatibility, in vitro drug release and in vivo wound healing studies. The results of NPs evaluation suggest the better stability and solubility of CUR. The nanohybrid scaffold showed good in vitro characteristics in terms of better water uptake, biocompatibility and sustained drug availability. The results of in vivo wound closure analysis revealed that nanohybrid scaffold treated wounds contracted significantly (p<0.001) faster than the wounds from the control and placebo scaffold groups. Further, the obtained results suggest that complete epithelialization with thick granulation tissue formation occur in nanohybrid scaffold group, whereas lack of compact collagen deposition in placebo scaffold group and presence of inflammatory cells in control group was observed. Hence, the present study suggests that the synergistic combination of CUR (anti-inflammatory and anti-oxidant), chitosan (sustain drug carrier, wound healing) and collagen (established wound healer as scaffold) is a promising strategy to address various pathological manifestations of diabetic wounds and have better wound healing capability.

Lidocaine Transdermal Patch: Pharmacokinetic Modeling and In Vitro-In Vivo Correlation (IVIVC).

The present study aims to develop the correlation between in vitro and in vivo skin permeation of lidocaine in its transdermal patch. In order to minimize the run-to-run variability during in vitro skin permeation studies, release normalized cumulative percent (%Ct n) was calculated. A suitable polynomial mathematical model was used to establish a correlation between time and %Ct n. Percent in vivo absorbed was calculated by using numerical deconvolution (NDC) and non-compartmental analysis (NCA) methods. Pharmacokinetic (PK) parameters such as AUC last and C max were predicted with the established in vitro-in vivo correlation (IVIVC) models. The minimum prediction errors in NDC method for C max were found to be -30.9 and -25.4% for studies I (in vivo study in human volunteers with one batch of Lidoderm patch; internal validation) and II (in vivo study in human volunteers with another batch of Lidoderm patch; external validation), respectively, whereas minimum prediction errors in NCA method were relatively low (3.9 and 0.03% for studies I and II, respectively) compared to those in NDC method. The prediction errors for AUC last were found to be less than 2% for both methods and studies. The established method in this study could be a potential approach for predicting the bioavailability and/or bioequivalence for transdermal drug delivery systems.

Current and emerging therapies in the management of diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcers are one of the major causes of mortality in diabetic patients. Very few drugs and therapies have regulatory approval for this indication and several agents from diverse pharmacological classes are currently in various phases of clinical trials for the management of diabetic foot ulcers. SCOPE: The purpose of this review is to provide concise information of the drugs and therapies which are approved and present in clinical trials. REVIEW METHODS: This review was carried out by systematic searches of relevant guidelines, patents, published articles, reviews and abstracts in PubMed/Medline, Web of Science, clinicaltrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Google Scholar of all English language articles up to 1 March 2015. The following search terms were used: diabetes, diabetic foot, diabetic foot ulcer, diabetic wound, diabetic foot infections, wound management, randomized controlled trials, approved treatments, new treatments and clinical trials. CONCLUSIONS: The various drugs and therapies for the management of diabetic foot ulcers comprise antibiotics, neuropathic drugs, wound dressings, skin substitutes, growth factors and inflammatory modulators. The majority of these therapies target the treatment of diabetic foot ulcers to address the altered biochemical composition of the diabetic wound. However, no single treatment can be definitively recommended for the treatment of diabetic foot ulcers.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Formulation and in vitro evaluation of rifampicin loaded porous microspheres.

Rifampicin (RIF) is a major component in fixed dose combination therapy for the treatment of tuberculosis. RIF has low solubility and high permeability with high dose and hence it is classified as class II drug in Biopharmaceutical Classification System (BCS). RIF has poor and variable bioavailability because of its poor solubility, acid decomposition and, drug and food interaction. The present investigation was aimed to develop RIF loaded porous microspheres as a controlled release dosage form. Eudragit based porous microspheres of RIF were prepared by emulsion solvent diffusion method. Prepared porous microspheres were evaluated for its entrapment efficacy, morphology, thermal behavior, crystalline nature, in-vitro drug release and stability in simulated gastric fluid. The entrapment efficacy of drug loaded microspheres was found to be in the range of 19.04â74.57%. Surface morphology revealed the porous and spherical structure of microspheres. Differential scanning calorimetric studies confirmed that formulation process altered the crystalline nature of RIF. In vitro drug release studies indicated that drug to polymer ratio of 2:1 showed more than 85% drug release over the period of 3 h. Stability studies in simulated gastric fluid (SGF) indicated that low relative decomposition of 18.5% was achieved with high drug to low polymer ratio of 1:4. The results obtained from the present investigation concluded that RIF loaded porous microspheres are suitable for developing oral controlled release dosage form of RIF that can prevent acid decomposition and provide better biopharmaceutical properties. Further more the microspheres can be evaluated for preventing the interaction with isoniazid, other drugs and foodstuffs.