Abstract
Background: The poor solubility of drugs is one of the most important limitations in formulating drugs into suitable dosage forms. In addition, the mechanical properties are the main obstacles in formulating tablet dosage form by direct compression method. Aim of this research: To investigate the possible improvement in mechanical properties, solubility performance, and tableting properties of drug-drug co-crystals of paracetamol and naproxen. Methods: The pre-compression parameters (Angle of repose, Carr’s index, and Hausner’s ratio) of the three paracetamol/naproxen co-crystals were investigated. Moreover, the solubility of the co-crystals was tested as well. In addition, the three paracetamol/naproxen co-crystals were formulated as oral tablets by direct compression method using microcrystalline cellulose and magnesium stearate. The prepared co-crystals were compressed into tablet dosage forms and the dissolution profiles were monitored. Results: The results showed an enhancement in flowability and compressibility of the prepared co-crystals when compared with paracetamol or naproxen alone. The poor tableting properties of prepared paracetamol tablets were very clear and they are in opposite to the co-crystals prepared tablets, which met all the pharmacopeial requirements. The in vitro dissolution study was conducted to compare the dissolution profiles of the prepared co-crystals tablets with marketed paracetamol tablets (Piodol®) and marketed naproxen tablets (Napron®). The dissolution profile of (1 to 2) co-crystal prepared tablets showed a superior dissolution rate with more than 50 % of the paracetamol drug dissolved within the first 5 minutes of dissolution rate. The dissolution study resulted in a better dissolution of the prepared paracetamol/naproxen tablets due to the co-crystal formation. Conclusion: It could be concluded that the prepared paracetamol/naproxen co-crystals represent a promising way for improving flowability and compression properties, enabling the formulation of the co-crystals as oral tablets by direct compression method with a clear enhancement in the dissolution rate.
Highlights
The thyroid gland secretes thyroxin (T4) and triiodothyroine (T3) hormones[1]
All animals were killed by cervical decapitation, the testes were dissected out, the right testis used to estimate the level of Malonaldehyde (MDA) which regard as marker for oxidative stress while the left testis was fixeԀ in Bouin׳s solution and processed through a series of alcohol dilutions and embedded in the paraffin wax to get sections of 5μm thickness which stained with hɑematoxylin-eosin (H&E) to be examined under the light microscope
Hypothyroidism is a clinical condition caused by reduction in the secretion of thyroid hormones from thyroid gland, it adversely affects the function of many organs including the reproductive function[21]
Summary
The thyroid gland secretes thyroxin (T4) and triiodothyroine (T3) hormones[1]. These hormones play a critical ᴦole in controlling the infant's brain and somatic Ԁdevelopment anԀ in the adult they regulate metabolic activity and the function of many organs[2]. Many organs in the body can be affected by thyroid dysfunction including male reproductive organ[9]. Hypothyroidism is a common thyroid disorder which influences the function of many organs including the reproductive organ Aim of this work: To examine the structural changes induced in the testis of adult male rats by hypothyroidism and the possible protective role of selenium. Testis of hypothyroid rats showed irregularity of some seminiferous tubule with thickening of their basement membrane, the diameter of seminiferous tubule and the height of germinal epithelium significantly decreased with decreases in the number of spermatocytes, Sertoli and Leydig cells. Rats of group IV showed significantly an improvement in hormonal level and histological structure of the testicular tissue compared to group II. Conclusion: hypothyroidism affects the structure of a testis but adding selenium has ameliorative role on thyroid function and histological changes of the testis
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