Investigating the physical stability of repackaged medicines stored into commercially available multicompartment compliance aids (MCAs).

BACKGROUND: Compliance aids are devices which have been developed and are currently used to assist individuals in their medicines management. The use of compliance aids involves the transfer of medicines from the manufacturers' original packaging and repackaged into an multicompartment compliance aid (MCA). MCAs do not guarantee the same level of protection compared to manufacturer's original packaging. OBJECTIVE: The aim of this study was to investigate the stability profile of atenolol, aspirin and lansoprazole dosage forms repackaged together in two different commercially available MCAs. METHODS: In a laboratory in the United Kingdom, the physical stability of the formulations repackaged into two commercially available brands of MCAs was evaluated. After 8 weeks of storage (under controlled ambient conditions), changes in the disintegration (tablets only) and dissolution properties (all formulations) were examined in accordance with British Pharmacopoeia (BP) specifications. KEY FINDINGS: Findings from this study confirm that changes in solid-dosage form quality are observed when repackaged into MCAs compared to manufacturers packaging resulting in differences in in-vitro dissolution performance. However, even with these changes, overall product performance was acceptable and within BP specifications. CONCLUSION: There is a need for greater collaboration in this area between manufacturers, hospital and community pharmacists, academics and policymakers to increase the data available on the physical stability and in turn performance of medicines repackaged into MCAs.

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning.

Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs.

Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats.

OBJECTIVES: A liposome preparation that is amenable to receptor-mediated endocytosis has been developed to enhance the oral bioavailability of poorly absorbable peptidomimetic drugs by use of folic acid as the mediator of liposomal uptake. METHODS: Folic acid was physically coupled to the surface of the liposomes and cefotaxime was used as the model drug. In-vivo evaluation was carried out on eight Sprague-Dawley rats in a two-way crossover study to compare the oral bioavailability of cefotaxime loaded in folic acid-free liposomes and folic acid-coupled liposomes. Blood samples were collected from the tail vein and plasma cefotaxime levels were determined using an HPLC method. KEY FINDINGS: Enhanced oral bioavailability (AUC(0-infinity)) of cefotaxime was observed when administered via folic acid-coupled liposomes. The peak plasma concentration (C(max)) of cefotaxime was increased when administered via folic acid-coupled liposomes as compared with folic acid-free liposomes. At 90% confidence interval, the value for AUC(0-infinity) was 1.4-2-times higher and the value for C(max) was 1.2-1.8-times higher for the folic acid-coupled liposomes compared with folic acid-free liposomes. CONCLUSIONS: Folic acid could enhance the uptake of liposomally entrapped drug. It could be a useful candidate to supplement liposome delivery systems.

Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes.

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.