Polylactide as a valuable biodegradable polymer is being widely investigated with respect to its synthesis, physical properties, biodegradation and application. The aim of this study is to evaluate hydrolytic degradation of poly (l-lactide) (PLLA) in the presence of added l-lactide dimer. High molecular weight PLLA was synthesized in presence of stannous octoate through the ring opening polymerization of l-lactide. PLLA films, containing 0, 1, 3 and 5% (w/w) l-lactide (as additive), were prepared by solution casting. In vitro degradation of the PLLA matrices were carried out in distilled water at 37°C for the definite periods. The degraded polymer matrices have been characterized by SEC, SEM and DSC techniques after periods of 3 and 6 months degradation time. It was found that during the first 3 months of degradation period, the number average molecular weight (¯Mn) of each PLLA film containing l-lactide reduced slower than the control sample. Also, it is shown that the films containing l-lactide have higher crystallinity and melting point in comparison with non-containing l-lactide samples. However, after 6 months, degradation rate of PLLA matrices containing l-lactide increased due to penetration of water by eluting and removal of l-lactide from PLLA matrices.

The effects of magnesium hydroxide and l-lactide dimer as additives on thermal properties and morphology of poly (l-lactide) (PLLA) films were studied. Hence, neat PLLA films and films containing additives (10% w/w) were prepared in dichloromethane at room temperature via solution casting. To evaluate thermal history on polymer properties, PLLA films were annealed by different processes. In one process, designated as A, PLLA films were heated from 20 up 140oC, then held for 1 h and cooled to room temperature. In another process, designated as B, melted PLLA samples which had been maintained at 200oC for 5 min were cooled with a rate of - 20oC/min to 140oC and annealed for 1 h before being cooled to room temperature. In the next process designated as C, the melted PLLA samples after 5 min of staying at 200oC were being quenched to 0oC. Then the samples were heated to 140oC followed by annealing for 1 h before being cooled to room temperature. The crystallization and morphology properties of PLLA films were studied using polarized optical microscopy and differential scanning calorimetry. It is found that the percentage of crystal and spherulitic formation inside PLLA films were influenced by thermal history and presence of the additives. The type of additives did not affect melting point (Tm) of the films annealed through different processes of A to C, while they had influence on Tm of the films, significantly. It is to be noted that some spherulites were formed in films during B process. During C process, however, the nucleation rate increased due to quenching which enhanced the spherulites formation.

Poly (L-lactide) is a chiral crystalline and biodegradable polymer. High molecular weight poly (L-lactide) is preferred in the production of surgical implant for internal fixation. These polymers are usually synthesized from L-lactide (cyclic di-ester of L-lactic acid). For the production of poly (L-lactide), bulk polymerization is the preferred procedure, but high temperature of the reaction may cause the thermal degradation of polymer. Therefore, optimizing the temperature and the duration time of the reaction for synthesis of high molecular weight polymer are very important. It is found that polymerization time and maximum molecular weight increase with decreasing reaction temperature, but when the reaction temperature is above the melting point of polymers, degradation is more extensive and faster, therefore, when the reaction temperature is set under the melting point of polymer the maximum molecular weight and the polymerization time are slightly changed. Glass transition temperature (Tg) and melting point (Tm) increased with increasing molecular weight. Tg and Tm of obtained polymers are 65-69°C and 160-180°C, respectively.

Lactide was synthesized by reverse polymerization of low molecular weight poly (lactic acid) with two different molecular weights: 1500 and 2500. Two different lactide purification processes such as: recrystallization in ethyl acetate and washing the crude lactide with ether before recrystallization in ethyl acetate were evaluated. It has been demonstrated that increasing the molecular weight of poly(lactic acid) does not influence the production yield, melting point and optical rotation of lactide. The washing of crude lactide with ether and recrystallization in ethyl acetate can be carried out in a short period of time (within 1 day) at a high yield (35%) using less solvent. In contrast, the first purification method gives lower (11%) production yield by using higher amount of solvent at longer time. It is also found that the purification methods do not have any specific effect on the properties of lactide.

This study investigates the thermal, morphological, mechanical, and biodegradation properties of blends comprising poly(L-lactide)-b-poly (ethylene glycol)-b-poly(L-lactide) triblock copolymer (PLLA-PEG-PLLA) and polypropylene (PP) compared to the PLLA/PP blends. All the blends were prepared using a melt-blending technique. The ability to crystallize and the thermal stability of the PLLA-PEG-PLLA were enhanced by blending PP, whereas these properties were not enhanced for the PLLA. The crystallinity of PLLA-PEG-PLLA increased from 20.4% to 23.5-38.8%. The temperature at maximum decomposition rate (Td,max) of PLLA end-blocks increased from 310 °C to 327-332 °C. The phase compatibility between the PLLA-PEG-PLLA and PP was better than between the PLLA and PP, as indicated by the smaller size of dispersed PP particles in the PLLA-PEG-PLLA matrix. The PLLA-PEG-PLLA/PP blends showed greater flexibility, higher wettability, and faster biodegradation rates than the PLLA/PP blends. This suggests that these PLLA-PEG-PLLA/PP blends may be used as flexible and partially biodegradable plastics.

The objective of this study was to compare the in vitro behavior of four long-acting subcutaneous risperidone formulations with in vivo performance, with the intent of establishing an IVIVC. Two copolymers of PLGA (50: 50 and 75: 25) were used to prepare four microsphere formulations of risperidone, an atypical antipsychotic. In vitro behavior was assessed at the physiological temperature (37 oC) using the ‘modified dialysis’ technique. The in vitro release profile demonstrated rank order behavior with Formulations A and B, prepared using the 50: 50 copolymer, exhibiting rapid drug release, while Formulations C and D, prepared using 75: 25 PLGA, released drug in a slower manner. In vivo profiles were obtained by two approaches, i.e., deconvolution using the Nelson–Wagner equation (the FDA recommended approach) and using fractional AUC. With both in vivo approaches, the 50: 50 PLGA preparations released drug faster than the 75: 25 PLGA microspheres, exhibiting the same rank order observed in vitro. Additionally, profiles for the four formulations obtained using the deconvolution approach were nearly superimposable with fractional AUC, implying that the latter procedure could be used as a substitute for the Nelson–Wagner method. A comparison of drug release profiles for the four formulations revealed that in three of the four formulations, in vivo release was slightly faster than that in vitro, but the results were not statistically significant (P>0.0001). An excellent linear correlation (R2 values between 0.97 and 0.99) was obtained when % in vitro release for each formulation was compared with its corresponding in vivo release profile, obtained by using fraction absorbed (Nelson–Wagner method) or fractional AUC. In summary, using the four formulations that exhibited different release rates, a Level A IVIVC was established using the FDA-recommended deconvolution method and fractional AUC approach. The excellent relationship between in vitro drug release and the amount of drug absorbed in vivo in this study was corroborated by the nearly 1: 1 correlation (R2 greater than 0.97) between in vitro release and in vivo performance. Thus, the results of the current study suggest that proper selection of an in vitro method to assess drug release from long-acting injectables will aid in obtaining a Level A IVIVC.