Strategic development and physicochemical analysis of oral preparations for unstable drugs

Oral liquid formulations are ideal dosage forms for paediatric, geriatric and patient with dysphagia. Dysphagia is prominent among patients suffering from stroke, motor neurone disease, advanced Alzheimer’s and Parkinson’s disease. However oral liquid preparations are particularly difficult to formulate for hydrophobic and unstable drugs. Therefore current methods employed in solving this issue include the use of ‘specials’ or extemporaneous preparations. In order to challenge this, the government has encouraged research into the field of oral liquid formulations, with the EMEA and MHRA publishing list of drugs of interest. The current work investigates strategic formulation development and characterisation of select API’s (captopril, gliclazide, melatonin, L-arginine and lansoprazole), each with unique obstacles to overcome during solubilisation, stabilisation and when developing a palatable dosage from. By preparing a validated calibration protocol for each of the drug candidates, the oral liquid formulations were assessed for stability, according to the ICH guidelines along with thorough physiochemical characterisation. The results showed that pH and polarity of the solvent had the greatest influence on the extent of drug solubilisation, with inclusion of antioxidants and molecular steric hindrance influencing the extent of drug stability. Captopril, a hydrophilic ACE inhibitor (160 mg.mL-1), undergoes dimerisation with another captopril molecule. It was found that with the addition of EDTA and HP-β-CD, the drug molecule was stabilised and prevented from initiating a thiol induced first order free radical oxidation. The cyclodextrin provided further steric hindrance (1:1 molar ratio) resulting in complete reduction of the intensity of sulphur like smell associated with captopril. Palatability is a crucial factor in patient compliance, particularly when developing a dosage form targeted towards paediatrics. L-arginine is extremely bitter in solution (148.7 g.L-1). The addition of tartaric acid into the 100 mg.mL-1 formulation was sufficient to mask the bitterness associated with its guanidium ions. The hydrophobicity of gliclazide (55 mg.L-1) was strategically challenged using a binary system of a co-solvent and surfactant to reduce the polarity of the medium and ultimately increase the solubility of the drug. A second simpler method was developed using pH modification with L-arginine. Melatonin has two major obstacles in formulation: solubility (100 μg.mL-1) and photosensitivity, which were both overcome by lowering the dielectric constant of the medium and by reversibly binding the drug within the cyclodextrin cup (1:1 ratio). The cyclodextrin acts by preventing UV rays from reaching the drug molecule and initiated the degradation pathway. Lansoprazole is an acid labile drug that could only be delivered orally via a delivery vehicle. In oral liquid preparations this involved nanoparticulate vesicles. The extent of drug loading was found to be influenced by the type of polymer, concentration of polymer, and the molecular weight. All of the formulations achieved relatively long shelf-lives with good preservative efficacy.

Typical performance of regular low-density parity-check codes over general symmetric channels

Typical performance of low-density parity-check (LDPC) codes over a general binary-input output-symmetric memoryless channel is investigated using methods of statistical mechanics. Relationship between the free energy in statistical-mechanics approach and the mutual information used in the information-theory literature is established within a general framework; Gallager and MacKay-Neal codes are studied as specific examples of LDPC codes. It is shown that basic properties of these codes known for particular channels, including their potential to saturate Shannon's bound, hold for general symmetric channels. The binary-input additive-white-Gaussian-noise channel and the binary-input Laplace channel are considered as specific channel models.

Low-complexity BCH codes with optimized interleavers for DQPSK systems with laser phase noise

The presence of high phase noise in addition to additive white Gaussian noise in coherent optical systems affects the performance of forward error correction (FEC) schemes. In this paper, we propose a simple scheme for such systems, using block interleavers and binary Bose–Chaudhuri–Hocquenghem (BCH) codes. The block interleavers are specifically optimized for differential quadrature phase shift keying modulation. We propose a method for selecting BCH codes that, together with the interleavers, achieve a target post-FEC bit error rate (BER). This combination of interleavers and BCH codes has very low implementation complexity. In addition, our approach is straightforward, requiring only short pre-FEC simulations to parameterize a model, based on which we select codes analytically. We aim to correct a pre-FEC BER of around (Formula presented.). We evaluate the accuracy of our approach using numerical simulations. For a target post-FEC BER of (Formula presented.), codes selected using our method result in BERs around 3(Formula presented.) target and achieve the target with around 0.2 dB extra signal-to-noise ratio.