BackgroundEffective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action.MethodsTherefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3.ResultsSignificantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups.ConclusionThese SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.

To treat anal fissure, internal anal sphincterotomy may be associated with surgical risks and incidence of incontinence. Botulinum toxin injection into the anal sphincter is invasive and expensive. Headache and hypotension hindered topical treatment with glyceryl trinitrate. Greater patient compliance, potentiated efficacy, reduced side effects, and lower cost are the major advantages offered by the combination therapy. Therefore, combination topical gels of nifedipine (NIF), lidocaine hydrochloride (LDH) and betamethasone valerate (BMV) were prepared and evaluated regarding viscosity, pH, drug content, and in vitro release. Compatibility study of drug–drug and drug-excipient mixtures preceded the formulation. Stability study was performed. A prospective randomized clinical trial was conducted for six weeks to assess the efficacy of the optimized formula in the treatment of anal fissure either acute (AAF, 37 patients) or chronic (CAF, 34 patients) in comparison with three single drug market products. The compatibility was indicated except in case of LDH with each of poloxamer 407 (P407), methylparaben, and propylparaben as well as BMV with P407. The gels showed acceptable viscosity ranges, tolerated pH values, and drugs content limits complying with the pharmacopeial limit. The gel containing 10% Transcutol® (F2) was selected as optimized formula due to the significant (p < 0.05) enhancement in NIF release. The recommended storage temperature was 8 °C. In comparison with the market products, the optimized gel can be represented as a potential combination therapy of acute and chronic anal fissures as suggested by significantly increased healing% and significantly reduced pain, bleeding, anal discharge and itching without side effects.

Background: The goal of this study was to develop a novel drug delivery system (NDDS) of lamivudine (LAM) to overcome some drawbacks associated with LAM short half-life. To fulfill this goal, polymeric LAM-loaded nanoparticles were prepared and their transdermal deliveries via passive and microneedles (MNs)-mediated transport were investigated. Methods: First, nanoparticles were prepared by double emulsion-solvent evaporation method using polylactic-co-glycolic acid (PLGA) and bovine serum albumin (BSA) as a polymer and a stabilizer respectively. Two different concentrations of LAM (10 and 20 mg/ml) were used for preparing LAM-loaded nanoparticles (NP 10 and NP 20 respectively). After that, the prepared nanoparticles were characterized with regard to their particle size (PZ), polydispersity index (PDI), zeta potential (ZP), percent yield (%Yield), morphology, drug loading capacity (%LC), and entrapment efficiency (%EE). Then, in vitro release of LAM from the LAM-loaded nanoparticles was studied and physical stability of the optimized LAM-loaded nanoparticles (NP 20) was examined. Finally, permeation of NP 20 and LAM solution across plain and MNs-treated excised rabbit skin was investigated. Results: The particle size of the prepared nanoparticles ranged from 152.87±1.27 nm to 196.67±1.74 nm, the PDI ranged from 0.089±0.01 to 0.145±0.03 and the ZP range was from-42.2±7.35 mV to-47.5±6.55 mV. All nanoparticles have distinct spherical shapes with smooth surface and thick shells of the BSA. The entrapment efficiencies of the LAM-loaded nanoparticles were 23.01±4.75% and 26.31±2.8%. A biphasic pattern of drug release was observed in the in vitro release studies with initially faster release profile followed by prolonged release for extended time. The physical stability assessment of NP 20 suspension showed that no significant variation of PZ, PDI and ZP could be detected during the storage period of six months. The steady state flux values of the LAM-loaded NP 20 across untreated skin and the MNs-treated skin were 7.49±1.46 µg.cm-2. hr-1 and 15.77±1.5 µg.cm-2. hr-1 respectively. Also, the permeation study showed the possibility of transdermal delivery of the LAM-loaded nanoparticles. In the same time, this delivery could be enhanced significantly by MNs-pretreatment of skin. The steady state flux of the LAM-loaded NP 20 across the MNs-treated skin was significantly greater than that of passive transport across untreated skin. Conclusions: Polymeric LAM-loaded nanoparticles could serve as a potential NDDS for the sustained transdermal delivery. The steady state flux could be enhanced by more than two folds using the MNsmediated transport.

A stable controlled release resinate-complex for the highly bitter taste famotidine (FAM) was developed to allow once-daily administration and improve patient compliance especially in pediatric and geriatric medicine. The drug-resinate complexes were prepared in different drug to resin (Amberlite IRP-69) ratios by weight (1:1, 1:2, 1:3, 1:4, 1:5 and 1:6). The optimized drug-resinate complex resulted from 1:6 drug to resin ratio experienced maximum drug loading and sustained release property. Hence, it was subjected to physicochemical characterizations by differential scanning colorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). The optimized complex was further dispensed in the prepared syrup and the suspension was subjected to accelerated stability study, as mentioned in the International Conference on Harmonization (ICH) guidelines. Furthermore, the gustatory properties of the complex were evaluated on humans. The syrup complied successfully with ICH guidelines and sufficiently alleviated the bitterness of famotidine.

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