This study provided a convenient approach for large scale production of hydrogenated soya phosphatidylcholine nano-liposome powders using beclometasone dipropionate as model drug and sucrose as proliposome carrier. Fluid-bed coating was employed to manufacture proliposomes by coating sucrose with the phospholipid (5%, 10%, 15% and 20% weight gains), followed by hydration, size reduction using high pressure homogenization, and freeze-drying to yield stable nano-vesicles. High pressure homogenization was compared with probe-sonication in terms of liposome size, zeta potential and drug entrapment. Furthermore, the effect of freeze-drying on vesicle properties generated using both size reduction methods was evaluated. Results have shown that high-pressure homogenization followed by freeze-drying and rehydration tended to yield liposomes smaller than the corresponding vesicles downsized via probe-sonication, and all size measurements were in the range of 72.64-152.50nm, indicating that f...

be avoided or minimized during the formulation process. Aqueous systems should be used rather than organic solvents. Additionally, any energy input such as shaking, vortexing, sonication, temperature increase, radiation, or ultrasound or changes in pH, ionic strength, salt concentration, buffer type, and solvent composition should be minimized to prevent the development of aggregation and eventually other degradation pathways.

The quality of a pharmaceutical dosage form is the foremost criterion during the development of a product. The quality by testing (QbT) technique used by the pharmaceutical industry to ensure the quality of a drug product is a rigid process with tight specifications. The specifications set by QbT are not essentially based upon the critical quality attributes of the materials and critical process parameters involved in development, but based upon recorded observation of manufactured batches. Room for flexibility is narrow as every level change requires submission of a supplement to the US Food Drug and Administration. Unlike QbT, the concept of quality by design (QbD) is a modern approach to ensure the quality of pharmaceutical products. It can identify the critical attributes of the material and the process parameters involved in development of the drug product through substantial scientific understanding with an established design space. QbD tools such as design of experiment, risk assessment, and process analytical technology help to establish a control strategy for every drug product with an option of continual monitoring and improvement for a quality drug product. Implementing the concept of QbD to topical dermatological dosage forms is in the initial stages. For a generic topical dermatological dosage form, establishing the required pharmaceutical and therapeutic equivalence with same components or qualitatively (Q1), same components with same concentration or quantitatively (Q2), and same components in same concentration with same arrangement (Q3) is a cumbersome process. Applying QbD approaches by defining a quality target product profile and identifying critical quality attributes with establishment of a design space and control strategy can guide the design of a quality-based generic topical dermatological product.

Objectives The aim of the study was to prepare a sublingual formulation for piroxicam using a thermosensitive polymer and to evaluate its permeation through porcine sublingual mucosa. Methods Formulation technique utilized the transition property of poloxamer from solution state at room temperature to gel state at oromucosal temperature (37 °C). The permeation of the drug was evaluated using an inverted Franz diffusion cell technique that allowed the dosage form to be directly applied onto the substrate with required volume of saliva. The formulation was characterized for microscopy of the piroxicam crystals, sol–gel transition property and in-vitro diffusion study. Key findings Poloxamer-based formulation enhanced solubility and increased permeability of the piroxicam. Conclusion Poloxamer formulation with 0.1% w/w piroxicam delivered a cumulative amount of 11.99 AE 7.82 and 11.23 AE 1.79 lg/cm 2 , while non-poloxamer formulation delivered 3.57 AE 2.20 and 4.60 AE 6.90 lg/cm 2 with 0.1 and 0.5 ml artificial saliva, respectively, through porcine sublingual tissue in 6 h. A similar delivery profile was observed for 0.05% w/w piroxicam formulation as well.

Novel in situ forming hydrogel microneedles were evaluated for transdermal drug delivery using a biocompatible non-ionic triblock amphiphilic thermosensitive copolymer. The transition property of poloxamer from solution at room temperature to gel at skin temperature (32 °C) was utilized in preparation of in situ forming hydrogel microneedles. Methotrexate has been used to treat solid tumors, but because of its narrow safety margin, it requires sustained delivery within the therapeutic window. Formulations with and without poloxamer at different methotrexate concentrations were prepared and evaluated for drug permeation across skin using vertical Franz diffusion cell for 72 h. Sol-gel transition, skin resistance and thickness, microneedles geometry, microchannel depth, shape, formation and uniformity, visco-elasticity of skin, and in vitro drug permeation were characterized and tested. An average cumulative drug amount of 32.2 ± 15.76 and 114.54 ± 40.89 μg/cm 2 for porcine ear skin and 3.89 ± 0.60 and 10.27 ± 6.98 μg/cm 2 for dermatomed human skin from 0.2 % w/w and 0.4 % w/w methotrexate formulations was delivered by the in situ forming hydrogel microneedles. These in situ hydrogel microneedles embedded within the porated site of the skin provided a steady and sustained drug delivery.

Several investigators have studied the drug-drug interaction that may exist when alcohol and H2-receptor antagonists (i.e. cimetidine, ranitidine, famotidine) are administered concomitantly. Results from these studies have been mixed. However, no systematic investigation of the change in blood alcohol concentrations in the social drinker versus the chronic drinker challenged by concurrent intake of alcohol and H2-receptor antagonist has been conducted. Eleven volunteers participated in this 14-day study. On day 0, study participants were administered an oral alcohol dose of 0.15 g/kg. On days 1 to 9, no medication was given. All volunteers then received cimetidine 400mg twice daily on days 10 to 13. On day 14, study participants received an oral alcohol dose of 0.15 g/kg after their morning dose of cimetidine. Blood sampling was performed on days 0 and 14 after alcohol administration. The comparative alcohol availabilities, pre-and post-cimetidine. were determined by comparing the time to peak plasma concentration (t max), peak plasma concentration (C max)' and the total area under the concentration-time curve (AUC). In the chronic drinkers. t max was significantly shorter than in the social drinkers following cimetidine administration (p = 0.008). Chronic drinkers who drink after cimetidine administration will have higher concentrations of alcohol faster than social drinkers. Medicolegal consequences resulting from this drug-drug interaction may occur; clinicians should therefore counsel patients about the possibility of enhanced impairment resulting from concurrent administration of these 2 drugs.