Factors involved in changes in the levator ani during pregnancy.

INTRODUCTION AND HYPOTHESIS: Levator ani muscle (LAM) dimensions increase during pregnancy to allow the delivery of the fetus. The objective was to investigate which factors are involved in LAM modifications during pregnancy. METHODS: A prospective longitudinal observational study was conducted between July 2015 and March 2018. Ninety-nine nulliparous pregnant women were included. Data on the physical examination, 4D transperineal ultrasound and hormonal concentrations (progesterone, oestradiol and relaxin) were collected during the first and third trimesters. RESULTS: We found higher hiatal dimensions at the beginning of pregnancy than in other studies with nonpregnant women. Increases in the levator ani hiatal (LH) dimensions were observed at contraction (1.01 ±1.96 cm2), rest (0.82 ± 2.51 cm2) and on Valsalva (2.36 ± 3.64 cm2) throughout pregnancy. The distensibility in the third trimester was higher than in the first trimester (5.79 vs 4.24 cm2; p=0); however, the contractility was lower (-3.32 vs -3.5 cm2; p=0.04). Women with lower scores on the Modified Oxford Grading Scale in the third trimester presented with lower contractility in the LAM. A larger LH at the end of pregnancy was associated with age and body mass index. Eleven women developed ballooning during pregnancy; in these women, relaxin was higher in both trimesters than in women without ballooning, but these results were not statistically significant. The linear models to predict third-trimester Valsalva LH, distensibility and contractility were not conclusive and did not show any factors to predict LAM modifications during pregnancy. CONCLUSIONS: Hormones could play a role in modifying the muscle properties of LAM from the beginning of pregnancy, but we did not find an association between LAM measurements and hormone concentration in this study.

Osmolality predictive models of different polymers as tools in parenteral and ophthalmic formulation development.

During the development of parenteral dosage forms, different physicochemical studies are required to ensure stable, effective and safe formulations. The osmolality of this kind of dosage forms should bear a close similarity to the body fluids to prevent local irritation, pain or even more significant side effects like endothelial damage. The osmotic studies performed in Polyethylene glycol 400 (PEG 400), Polyethylene glycol 4000 (PEG 4000), Poloxamer 407 (P407), Sodium Hyaluronate (SH), Chondroitin Sulphate Sodium (CS), Cremophor RH 40 (CRE40) and Polyvinyl alcohol (PVA) aqueous solutions, showed that the theoretical determination of the osmolality based on their molecular weight as the only determinant factor did not agree with the values obtained by the measurement of colligative properties such as the freezing point depression. The data obtained from this study and its analysis, provided predictive equations that can be used as tools in the primary development to estimate formulation's osmolality at different concentrations; and its evolution over a period at the hypothetical worst-case scenario of storage temperature.

A new design for the review and appraisal of semi-solid dosage forms: Semi-solid Control Diagram (SSCD).

The Semi-solid Control Diagram (SSCD) is a new tool designed for the study of different excipients and different semi-solid dosage forms. It can be used to review and evaluate different formulations and/or batches and facilitate the selection of one of them that will present the most suitable galenic characteristics for topical application. It is also useful to track stability studies by comparing the diagrams, which allows to measure the impact of subjecting the formulation to different conditions and times to be examined. In this study, the Semi-solid Control Diagram (SSCD) is used as an instrument for studying and evaluating semi-solid pharmaceutical dosage forms, by comparing several different semisolid preparations (lipogels). With these results, the tool is validated and the best formulation has been discriminated from the others.

Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant.