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Oral colon delivery systems based on a dual targeting strategy, harnessing time- and microbiota-dependent release mechanisms, were designed in the form of a drug-containing core, a swellable/biodegradable polysaccharide inner layer and a gastroresistant outer film. High-methoxyl pectin was employed as the functional coating polymer and was applied by spray-coating or powder-layering. Stratification of pectin powder required the use of low-viscosity hydroxypropyl methylcellulose in water solution as the binder. These coatings exhibited rough surfaces and higher thicknesses than the spray-coated ones. Using a finer powder fraction improved the process outcome, coating quality and inherent barrier properties in aqueous fluids. Pulsatile release profiles and reproducible lag phases of the pursued duration were obtained from systems manufactured by both techniques. This performance was confirmed by double-coated systems, provided with a Kollicoat® MAE outer film that yielded resistance in the acidic stage of the test. Moreover, HM pectin-based coatings manufactured by powder-layering, tested in the presence of bacteria from a Crohn's disease patient, showed earlier release, supporting the role of microbial degradation as a triggering mechanism at the target site. The overall results highlighted viable coating options and in vitro release characteristics, sparking new interest in naturally occurring pectin as a coating agent for oral colon delivery. [ABSTRACT FROM AUTHOR]

Retentive drug delivery systems (DDSs) are intended for prolonged residence and release inside hollow muscular organs, to achieve either local or systemic therapeutic goals. Recently, formulations based on shape memory polymers (SMPs) have gained attention in view of their special ability to recover a shape with greater spatial encumbrance at the target organ (e.g., urinary bladder or stomach), triggered by contact with biological fluids at body temperature. In this work, poly(vinyl alcohol) (PVA), a pharmaceutical-grade SMP previously shown to be an interesting 4D printing candidate, was employed to fabricate expandable organ-retentive prototypes by hot melt extrusion. With the aim of improving the mechanical resistance of the expandable DDS and slowing down relevant drug release, the application of insoluble permeable coatings based on either Eudragit® RS/RL or Eudragit® NE was evaluated using simple I-shaped specimens. The impact of the composition and thickness of the coating on the shape memory, swelling, and release behavior as well as on the mechanical properties of these specimens was thoroughly investigated and the effectiveness of the proposed strategy was demonstrated by the results obtained. [ABSTRACT FROM AUTHOR]

Despite poor absorption properties, delivery to the colon of bioactive compounds administered by the oral route has become a focus of pharmaceutical research over the last few decades. In particular, the high prevalence of Inflammatory Bowel Disease has driven interest because of the need for improved pharmacological treatments, which may provide high local drug concentrations and low systemic exposure. Colonic release has also been explored to deliver orally biologics having gut stability and permeability issues. For colon delivery, various technologies have been proposed, among which time-dependent systems rely on relatively constant small intestine transit time. Drug delivery platforms exploiting this physiological feature provide a lag time programmed to cover the entire small intestine transit and control the onset of release. Functional polymer coatings or capsule plugs are mainly used for this purpose, working through different mechanisms, such as swelling, dissolution/erosion, rupturing and/or increasing permeability, all activated by aqueous fluids. In addition, enteric coating is generally required to protect time-controlled formulations during their stay in the stomach and rule out the influence of variable gastric emptying. In this review, the rationale and main delivery technologies for oral colon delivery based on the time-dependent strategy are presented and discussed. [ABSTRACT FROM AUTHOR]

To overcome difficulties in splitting, uneven breaking and inconsistent dosing frequently reported with scored tablets, a novel punch was proposed for the manufacturing of easy breakable tablets (EBTs). In this work, the performance of the EBT punch was investigated vs. a ridged one for traditional breakable tablets (TBTs) using a furosemide powder formulation for orally disintegrating tablets (ODTs). A Face Centered Central Composite Design was applied to investigate the influence of punch type, compaction force, tablet weight and press rotation speed on the mechanical properties of ODTs, their behavior in aqueous fluids and aptitude for splitting. Mass uniformity and adequate crushing strength, friability, water uptake, disintegration and wetting times were obtained from both TBTs and EBTs. Interestingly, more favorable splitting behavior was shown by tablets manufactured by the novel punch, in view of lower mass loss and portion mass variability after breaking. The ease of breaking, accuracy of subdivision and mass loss of ODTs were also evaluated by a volunteer (n = 20) panel test. Less difficulty was found in splitting EBTs than TBTs (p < 0.05), and a larger number of tablets were properly broken into four parts. Thus, this study proved the usefulness of the EBT punch in overcoming drawbacks associated with divisible tablets. [ABSTRACT FROM AUTHOR]

A swellable/erodible system for oral time-dependent release, demonstrated to provide consistent pulsatile and colonic delivery performance, has been manufactured through a range of coating techniques to achieve the functional hydroxypropyl methylcellulose (HPMC) layer. Although aqueous spray-coating has long been preferred, the processing times and yields still represent open issues, especially in view of the considerable amount of polymer required to give in vivo lag phases of proper duration. To make manufacturing of the delivery system more cost-efficient, different coating modes were thus evaluated, namely top and tangential spray-coating as well as powder-layering, using a fluid bed equipment. To this aim, disintegrating tablets of 5 mm in diameter, containing a tracer drug, were coated up to 50% weight gain with low-viscosity HPMC, either as a water solution or as a powder formulation. In all cases, process feasibility was assessed following setup of the operating conditions. Irrespective of the technique employed, the resulting dosage forms exhibited uniform coating layers able to defer the onset of release as a function of the amount of polymer applied. The structure and thickness of such layers differed depending on the deposition modes. With respect to top spray-, both tangential spray-coating and powder-layering were shown to remarkably ameliorate the process time, which was reduced to approximately 1/3 and 1/6, and to enhance the yield by almost 20 and 30%, respectively. Clear advantages associated with such techniques were thus highlighted, particularly with respect to powder-layering here newly proposed for application of a swellable hydrophilic cellulose derivative. [ABSTRACT FROM AUTHOR]

Retentive drug delivery systems are intended for prolonged residence and release inside hollow organs of the body, in pursuit of either local or systemic therapeutic goals. Because of the relatively long‐lasting period of time they could cover during operation, a primary advantage arising from their use would lie in reduced dosing frequency, thereby improving the overall adherence of patients to prescribed medication regimens. The treatment of numerous pathologies that affect the urinary bladder and the stomach could especially benefit from viability of such delivery technologies. Moreover, by making use of effective gastroretentive dosage forms, the bioavailability of drugs that are preferably absorbed from the upper gastrointestinal tract could be increased. Expansion of devices following administration is often exploited for retention purposes, and several formulation strategies have been proposed in this respect. Innovative applications of shape memory materials have also been explored, highlighting the great inherent potential for facing the challenges involved. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48798. [ABSTRACT FROM AUTHOR]

Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms. [ABSTRACT FROM PUBLISHER]

A multiple-unit formulation for time-dependent colonic release of insulin was obtained by coating insulin and sodium glycocholate immediate-release minitablets with: (i) Methocel® E50, a low-viscosity hydroxypropyl methylcellulose (inner coating), (ii) 5:1 w/w Eudragit® NE/Explotab® V17, a mixture of a neutral polymethacrylate with a pore-forming superdisintegrant (intermediate coating), and (iii) Aqoat® AS, enteric-soluble hydroxypropyl methylcellulose acetate succinate (outer coating). Sodium glycocholate was added as a permeation enhancer while the inner, intermediate and outer coatings were aimed, respectively, at delaying the onset of release through swelling/erosion processes, extending the duration of the lag phase by slowing down water penetration into the underlying functional layer, and overcoming variable gastric residence time. In vitro studies showed that neither insulin nor sodium glycocholate were released from the three-layer system during 2 h of testing in 0.1 N HCl, while complete release of the protein and of the enhancer occurred in phosphate buffer, pH 6.8, after consistent lag phases. No significant changes were noticed in the release profiles following twelve-month storage at 4 °C. Oral administration of the novel formulation to diabetic rats elicited a peak in the plasma insulin concentration after 6 h, which was associated with a sharp decrease in the glycemic levels. The relative bioavailability and pharmacological availability of such a formulation, as determined vs. the uncoated tablets, were 2.2 and 10.3, respectively. Based on these results, the three-layer system presented was considered a potentially interesting tool for oral colonic delivery of insulin and adjuvant compounds. [ABSTRACT FROM AUTHOR]

The aim of this work was to prepare and evaluate an oral dosage form intended for time-dependent colon delivery of insulin along with a selected protease inhibitor (camostat mesilate) and absorption enhancer (sodium glycocholate). A previously described release platform, which had proven potentially suitable for the protein delivery, was exploited. Insulin compatibility with the above-mentioned adjuvants was preliminarily evaluated. For this purpose, the drug and its main degradation products were assayed by HPLC in insulin powder mixtures with camostat mesilate and/or sodium glycocholate stored 12 months at 4°C. No significant decrease in protein content or increase in degradation product percentages beyond Eur. Ph. 6th Ed. limits was highlighted. Moreover, calorimetric studies performed on physical and compacted binary insulin mixtures with camostat mesilate and sodium glycocholate showed that the thermal behavior of both adjuvants was unchanged. Subsequently, tablet cores with differing compositions were prepared and spray-coated with an aqueous HPMC solution in order to obtain pulsatile delivery systems. The coated units were demonstrated to concurrently release the drug and the adjuvants in a prompt and quantitative mode after consistent lag times. Based on these results, the device was proven a potential candidate for colon delivery of insulin and the selected adjuvants. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4661–4669, 2009 [ABSTRACT FROM AUTHOR]

Dry coating is an innovative powder-layering technique that enables the formation of coatings on solid dosage forms with no need for using water or organic solvents. This technique envisages the distribution of polymer powder blends onto substrate cores and the concurrent or alternate nebulization of liquid plasticizers. In this work, a dry coating process based on hydroxypropyl methylcellulose acetate succinate (HPMCAS) was set up in a rotary fluid bed equipment to prepare enteric-coated soft gelatin capsules. Promising results were obtained in terms of process feasibility and product characteristics, thus suggesting the possibility of advantageous applications for the investigated technique when dealing with gelatin capsule substrates. [ABSTRACT FROM AUTHOR]

Partially coated perforated systems (PCPS) based on low-viscosity hydroxypropyl methylcellulose (HPMC) as the polymeric material were formerly designed, prepared and evaluated in terms of in vitro behaviour. These systems proved to afford the pursued linear release with model drugs (metoprolol tartrate and benfluorex) of different solubility. To the aim of exploring the mechanisms concurring in the definition of zero-order kinetics, studies of drug release, polymer dissolution and medium penetration were performed on PCPS and constant release area systems (CRAS). According to the obtained results, PCPS release kinetics has to be mainly attributed to the progressive outward erosion of the core and to the related variation of the release area. The special geometry of the system, in fact, involves a gradual increase in the release surface, which allows the diffusional path lengthening to be offset. By properly selecting the shape and dimensions of the device as well as the physico-chemical characteristics of the hydrophilic polymer, the advantage of a zero-order release kinetics with programmable rate can be achieved. [Copyright &y& Elsevier]

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics. The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one. [ABSTRACT FROM AUTHOR]